Pandemic Considerations on Essential Oral Health Care.

The coronavirus disease 2019 (COVID-19) pandemic revealed a lack of consensus on the concept of essential oral health care. We propose a definition of essential oral health care that includes urgent and basic oral health care to initiate a broader debate and stakeholder alignment. We argue that oral health care must be part of essential health care provided by any health system. Essential oral health care covers the most prevalent oral health problems through an agreed-on set of safe, quality, and cost-effective interventions at the individual and community level to promote and protect oral health, as well as prevent and treat common oral diseases, including appropriate rehabilitative services, thereby maintaining health, productivity, and quality of life. By default, essential oral health care does not include the full spectrum of possible interventions that contemporary dentistry can provide. On the basis of this definition, we conceptualize a layered model of essential oral health care that integrates urgent and basic oral health care, as well as advanced/specialist oral health care. Finally, we present 3 key reflections on the essentiality of oral health care. First, oral health care must be an integral component of a health care system's essential services, and by implication, oral health care personnel are part of the essential health care workforce. Second, not all dental care is essential oral health care, and not all essential care is also urgent, particularly under the specific risk conditions of the pandemic. Third, there is a need for criteria, evidence, and consensus-building processes to define which dental interventions are to be included in which category of essential oral health care. All stakeholders, including the research, academic, and clinical communities, as well as professional organizations and civil society, need to tackle this aspect in a concerted effort. Such consensus will be crucial for dentistry in view of the Sustainable Development Goal's push for universal health coverage, which must cover essential oral health care.

Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

Quality Appraisal of Child Oral Health-Related Quality of Life Measures: A Scoping Review.

BACKGROUND: Children's oral health-related quality of life (COHQoL) measures are well known and widely used. However, rigorous systematic reviews of these measures and analyses of their quality are in absence. OBJECTIVES: To systematically review and quantitatively assess the quality of COHQoL measures through a scoping review. DATA SOURCES: Systematic literature search of PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE (Excerpta Medica database), HaPI (Health and Psychosocial Instruments), and DOSS (Dentistry and Oral Sciences Source). STUDY ELIGIBILITY: The measure's focus was COHQoL; the child age ranged from 5 to 14 years; the publication was either a research article or a systematic review and related to caries; and it was written in English or had an English abstract. Two authors independently selected the studies. Disagreements were reconciled by group discussions with a third author. APPRAISAL: The International Society for Quality of Life Research minimum standards for patient-reported outcome measures were used for quality appraisal. SYNTHESIS: Descriptive analysis. RESULTS: We identified 18 measures. Their quality scores ranged from 9.5 to 15.0 on a scale of 16. The quality appeared to bear no relationship to the citation and use of these measures. However, elements of these measures might be more useful than others, depending on the age-specific use and primary quality concerns. LIMITATIONS: Some of the information on the minimum standards of the 18 measures cannot be found in the existing literature. Measures published without English abstract were not searched. CONCLUSIONS: The quality of these measures is suboptimal. Researchers and practitioners in this field should exercise caution when choosing and using these measures. Efforts at improving the quality of the COHQoL measures, such as refining existing ones or developing new measures, are warranted. KNOWLEDGE TRANSFER STATEMENT: Researchers, clinician scientists, and clinicians can use the results of this study when deciding which oral health-related quality of life measure they wish to use in children.

An Economic Evaluation of a Comprehensive School-Based Caries Prevention Program.

INTRODUCTION: Current economic evaluations of school-based caries prevention programs (SCPPs) do not compare multiple types of SCPPs against each other and do not consider teeth beyond permanent first molars. OBJECTIVES: To assess the cost-effectiveness of a comprehensive SCPP relative to an SCPP focused on delivering sealants for permanent first molars only and to a default of no SCPP. Based on a societal perspective, a simulation model was used that compared the health and cost impacts on 1) permanent first molars only and 2) all posterior teeth. METHODS: To calibrate the model, we used data from CariedAway, a comprehensive SCPP that used glass ionomer to prevent and arrest active decay among children. We then evaluated the incremental cost-effectiveness of implementing 3 alternate school-based approaches (comprehensive, sealant only, and no program) on only first molars and all posterior teeth. Probabilistic, 1-, and 2-way sensitivity analyses are included for robustness. Cost-effectiveness is assessed with a threshold of $54,639 per averted disability-adjusted life year (DALY). RESULTS: We first compared the 3 programs under the assumption of treating only first molars. This assessment indicated that CariedAway was less cost-effective than school-based sealant programs (SSPs): the resulting incremental cost-effectiveness ratio (ICER) for CariedAway versus SSPs was $283,455 per averted DALY. However, when the model was extended to include CariedAway's treatment of all posterior teeth, CariedAway was not only cost-effective but also cost-saving relative to SSPs (ICER, -$943,460.88 per averted DALY; net cost, -$261.45) and no SCPP (ICER, -$400,645.52 per averted DALY; net cost, -$239.77). CONCLUSIONS: This study finds that economic evaluations assessing only cost and health impacts on permanent first molars may underestimate the cost-effectiveness of comprehensive SCPPs 1) preventing and arresting decay and 2) treating all teeth. Hence, there is an urgent need for economic evaluations of SCPPs to assess cost and health impacts across teeth beyond only permanent first molars. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by policy makers to understand how to evaluate economic evaluations of school-based caries prevention programs and what factors to consider when deciding on what types of programs to implement.

School-Based Caries Prevention, Tooth Decay, and the Community Environment.

The school and community context can contribute to inequity in child oral health. Whether the school and community affect the effectiveness of school-based caries prevention is unknown. The association between the school and community environment and dental caries, as well as their moderating effects with school-based caries prevention, was assessed using multilevel mixed-effects regression. Data were derived from a 6-y prospective cohort study of children participating in a school-based caries prevention program. For the school and community, living in a dental-shortage area and the proportion of children receiving free or reduced lunch were significantly related to an increased risk of dental caries at baseline. Caries prevention was associated with a significant per-visit decrease in the risk of untreated caries, but the rate of total caries experience increased over time. Caries prevention was more effective in children who had prior dental care at baseline and in schools with a higher proportion of low socioeconomic status students. There was significant variation across schools in the baseline prevalence of dental caries and the effect of prevention over time, although effects were modest. The school and community environment have a direct impact on oral health and moderate the association between school-based caries prevention and dental caries. Knowledge Transfer Statement: School-based caries prevention can be an effective means to reduce oral health inequity by embedding dental care within schools. However, the socioeconomic makeup of schools and characteristics of the surrounding community can affect the impact of school-based care.

European Fissure Sealant Guidelines: assessment using AGREE II.

BACKGROUND: Pit and fissure sealants are effective in reducing the incidence of occlusal caries, and multiple clinical practice guidelines (CPGs) have been developed for recommending their proper use. The usefulness of CPGs depends on their quality and on the rigour of the guideline development process. OBJECTIVE: A study was made to assess the quality of current European CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, which uses 23 key items rated on a 7-point scale to assess practice guideline development and the quality of reporting. METHODS: A search was conducted for fissure sealant guidelines for preventing caries in children and adults at high and low risk published in the last 10 years. Calibration was carried out before scoring to assess agreement between the appraisers using the AGREE II instrument. RESULTS: The searches identified 19 relevant guidelines, and following application of the inclusion/exclusion criteria, three guidelines were retained for evaluation. The proportion of observed agreement was calculated, expressed by the agreement separately for positive and negative ratings (PA = 0.89, NA = 0-91). The results of the guideline assessments revealed the highest score for the Irish guideline, a moderate score for the French guideline and the lowest score for the European guideline. CONCLUSIONS: Based on the AGREE II instrument, the results obtained show significant variation in the quality assessment of the three European Fissure Sealant Guidelines. Future studies should be carried out both to develop quality dental CPGs and to investigate effective ways of adopting them.

Energy transfer properties of Rhodobacter sphaeroides chromatophores during adaptation to low light intensity.

Time-resolved fluorescence spectroscopy was used to explore the pathway and kinetics of energy transfer in photosynthetic membrane vesicles (chromatophores) isolated from Rhodobacter (Rba.) sphaeroides cells harvested 2, 4, 6 or 24 hours after a transition from growth in high to low level illumination. As previously observed, this light intensity transition initiates the remodeling of the photosynthetic apparatus and an increase in the number of light harvesting 2 (LH2) complexes relative to light harvesting 1 (LH1) and reaction center (RC) complexes. It has generally been thought that the increase in LH2 complexes served the purpose of increasing the overall energy transmission to the RC. However, fluorescence lifetime measurements and analysis in terms of energy transfer within LH2 and between LH2 and LH1 indicate that, during the remodeling time period measured, only a portion of the additional LH2 generated are well connected to LH1 and the reaction center. The majority of the additional LH2 fluorescence decays with a lifetime comparable to that of free, unconnected LH2 complexes. The presence of large LH2-only domains has been observed by atomic force microscopy in Rba. sphaeroides chromatophores (Bahatyrova et al., Nature, 2004, 430, 1058), providing structural support for the existence of pools of partially connected LH2 complexes. These LH2-only domains represent the light-responsive antenna complement formed after a switch in growth conditions from high to low illumination, while the remaining LH2 complexes occupy membrane regions containing mixtures of LH2 and LH1-RC core complexes. The current study utilized a multi-parameter approach to explore the fluorescence spectroscopic properties related to the remodeling process, shedding light on the structure-function relationship of the photosynthetic assembles. Possible reasons for the accumulation of these largely disconnected LH2-only pools are discussed.

Global oral health inequalities: dental caries task group--research agenda.

The IADR Global Oral Health Inequalities Task Group on Dental Caries has synthesized current evidence and opinion to identify a five-year implementation and research agenda which should lead to improvements in global oral health, with particular reference to the implementation of current best evidence as well as integrated action to reduce caries and health inequalities between and within countries. The Group determined that research should: integrate health and oral health wherever possible, using common risk factors; be able to respond to and influence international developments in health, healthcare, and health payment systems as well as dental prevention and materials; and exploit the potential for novel funding partnerships with industry and foundations. More effective communication between and among the basic science, clinical science, and health promotion/public health research communities is needed. Translation of research into policy and practice should be a priority for all. Both community and individual interventions need tailoring to achieve a more equal and person-centered preventive focus and reduce any social gradient in health. Recommendations are made for both clinical and public health implementation of existing research and for caries-related research agendas in clinical science, health promotion/public health, and basic science.

Silver diamine fluoride: a caries "silver-fluoride bullet".

The antimicrobial use of silver compounds pivots on the 100-year-old application of silver nitrate, silver foil, and silver sutures for the prevention and treatment of ocular, surgical, and dental infections. Ag(+) kills pathogenic organisms at concentrations of <50 ppm, and current/potential anti-infective applications include: acute burn coverings, catheter linings, water purification systems, hospital gowns, and caries prevention. To distill the current best evidence relative to caries, this systematic review asked: Will silver diamine fluoride (SDF) more effectively prevent caries than fluoride varnish? A five-database search, reference review, and hand search identified 99 human clinical trials in three languages published between 1966 and 2006. Dual review for controlled clinical trials with the patient as the unit of observation, and excluding cross-sectional, animal, in vitro studies, and opinions, identified 2 studies meeting the inclusion criteria. The trials indicated that SDF's lowest prevented fractions for caries arrest and caries prevention were 96.1% and 70.3%, respectively. In contrast, fluoride varnish's highest prevented fractions for caries arrest and caries prevention were 21.3% and 55.7%, respectively. Similarly, SDF's highest numbers needed to treat for caries arrest and caries prevention were 0.8 (95% CI=0.5-1.0) and 0.9 (95% CI=0.4-1.1), respectively. For fluoride varnish, the lowest numbers needed to treat for caries arrest and prevention were 3.7 (95% CI=3.4-3.9) and 1.1 (95% CI=0.7-1.4), respectively. Adverse events were monitored, with no significant differences between control and experimental groups. These promising results suggest that SDF is more effective than fluoride varnish, and may be a valuable caries-preventive intervention. As well, the availability of a safe, effective, efficient, and equitable caries-preventive agent appears to meet the criteria of both the WHO Millennium Goals and the US Institute of Medicine's criteria for 21st century medical care.

Introduction to cumulative meta-analysis in dentistry: lessons learned from undertaking a cumulative meta-analysis in periodontology.

Improving health and well-being from the consideration of isolated studies is problematic. Systematic reviews have been developed to address this problem and may include a quantitative data synthesis in the form of a meta-analysis, or a cumulative meta-analysis. The value of systematic reviews depends greatly on the availability and quality of the results of primary research. The objective of the current project was to demonstrate the technique of cumulative meta-analysis in dentistry using data from a previously published systematic review. The process highlights an issue that some trials could not be synthesized due to the lack of reporting of measures of variation. This represents a potential source of bias. Investigators are encouraged to consider their trials as part of an information continuum and to report sufficient detail to permit the trials' incorporation into subsequent syntheses.

Oral epithelial overexpression of IL-1alpha causes periodontal disease.

Periodontal disease is a bacterial infection that results in inflammatory destruction of tissues that support the teeth, including connective tissue and bone. In this study, we report that transgenic mice that overexpress the 17-kDa form of IL-1alpha in the basal layer of oral mucosal epithelium develop a syndrome that possesses all of the cardinal features of periodontal disease, including epithelial proliferation and apical migration, loss of attachment, and destruction of cementum and alveolar bone. In this model, bacterial colonization and infection were not required, since levels of periodontal bacteria were equivalent in transgenic and wild-type mice, and continuous treatment with antibiotics from birth did not ameliorate the disease. Our findings therefore indicate that elevated levels of IL-1alpha in the oral micro-environment can mediate all of the clinical features of periodontal disease.

A systematic review of in vivo retrograde obturation materials.

PURPOSE: The aim of this study was to answer the question: For patients requiring apicoectomy (apicectomy/root-end resection) and retrograde (root-end) obturation (filling), which retrograde obturation (root-end filling) material(s) is/are the most effective, as determined by reduction in periapical radiolucency and elimination of signs and symptoms? MATERIALS AND METHODS: A MEDLINE and a Cochrane search (two specified searches) were conducted to identify randomised (RCT) and nonrandomised controlled clinical trials (CCT), cohort studies (CS) and case-control studies (CCS), published between 1966 and 2002, October week 4, conducted on humans, and published in English, German and French language, relating to retrograde obturation materials following apicoectomy. RESULTS: The MEDLINE and the Cochrane search identified 324 and 21 published articles, respectively. The Cochrane search identified three additional articles to the MEDLINE-search articles. Fourteen studies met the inclusion criteria: two were RCTs, six were CCTs, none was a CS and six were retrospective CCSs. Nine of the 14 studies compared a new retrograde (root-end)-filling material to amalgam, 4 of the 14 studies compared orthograde root canal fillings to retrograde (root-end) amalgam and the fourteenth study compared variations of a resin composite (Retroplast) when used in combination with the bonding agent Gluma (Bayer AG, Gluma 1 and 2). The two RCTs indicated that glass ionomer cement appeared to be equivalent to amalgam. The six CCTs indicated that orthograde filling with gutta-percha and sealer was more effective than amalgam retrograde (root-end)-filling (one trial). Similarly, retrograde (root-end)-filling with (i) composite and Gluma (Bayer AG, Leverkusen, Germany) as bonding agent (one trial), (ii) reinforced zinc oxide eugenol cement (EBA cement) (Stailine, Staident, Middlesex, England; one trial) and (iii) gold leaf (one trial) appeared to be better than amalgam retrograde (root-end)-filling. Finally, gutta-percha retrograde (root-end)-filling appears to be less effective than amalgam (one trial) and Retroplast with ytterbium trifluoride is better than Retroplast with silver, when they are both used with Gluma as bonding agent (one trial). CONCLUSIONS: For the highest level of evidence (RCT) retrograde (root-end)-filling with glass ionomer cement is almost as effective as amalgam. However, there was a significant caveat as there were only two RCTs. At the next highest level of evidence (CCT), and given the additional caveat that there was only one controlled trial for each material, retrograde (root-end) EBA cement, composite with Gluma and gold leaf, as well as orthograde gutta-percha, may be more effective than retrograde (root-end) amalgam filling. In conclusion, these results suggest that additional validating CCTs and RCTs are needed.

A bibliometric analysis of the pediatric dental literature in MEDLINE.

PURPOSE: The purpose of this study was to estimate the availability of dental literature between 1989 and 1998 in seven disciplines within pediatric dentistry by using a bibliometric analysis on MEDLINE and to compare the results to that for adolescents and adults. METHODS: A search strategy was developed for each discipline incorporating dental vocabulary obtained from the MEDLINE Medical Subject Heading (MeSH) index. The number of articles retrieved from MEDLINE for adolescents and adults (> 13 yo) was compared to those for children (< 12 yo) in seven dental disciplines: dental implants, endodontics, oral medicine/radiology, oral surgery, orthodontics, periodontics, and restorative dentistry. RESULTS: There was an average of 8,097 dental articles published each year for the combined seven disciplines studied with an eight-fold range from 327 articles/year for endodontics to 2,765 articles/year for oral medicine/radiology. Of the mean number of articles published each year, 1,273 (16%) were limited to children, while the remaining 6,824 (84%) were on adolescents and adults. The number and percentage of children articles relative to the total number of publications on children ranged from 7 articles/year (1%) for dental implants to 528 articles/year (42%) for oral medicine/radiology. Implant dentistry publications increased the fastest, growing at an average yearly rate of 25%, followed by restorative dentistry (9%), endodontics (9%), oral surgery (6%), orthodontics (6%), periodontics (3%), and oral medicine/radiology (2%). CONCLUSIONS: There is a substantial amount of literature in pediatric dentistry upon which to base clinical decisions. Within this large body of literature, there is a significant amount of variation between the various dental disciplines examined. To stay current, one would need to read and absorb approximately 24 articles each week over 52 weeks per year in more than 75 different journals. Furthermore, the volume of literature is increasing each year, making access even more difficult. These trends suggest the need for computer systems that will facilitate access and retrieval of clinically useful literature.

Benchmarking the endodontic literature on MEDLINE.

The purpose of this study was to identify and quantify the endodontic literature available for clinical decision making. A search strategy based on Medical Subject Headings for endodontics was developed to examine MEDLINE. The identified articles were limited to human subjects and English. Sensitive and specific methodological search filters identified four categories of information: etiology, diagnosis, therapy, and prognosis. The results were then subdivided by year to identify trends. Between 1990 and 1998 MEDLINE identified 3,152 articles published in English on endodontics in humans. The number of articles per year (mean +/- SD) for sensitive and specific searches was etiology (28+/-10, 1+/-2), diagnosis (38+/-11, 1+/-1), therapy (59+/-15, 3+/-3), and prognosis (40+/-13, 10+/-5), respectively. The number of articles in each category increased by 1 to 3% each year. There were 150 articles/yr in endodontics in at least 120 journals cited on MEDLINE on which to base clinical decisions.

Variation, certainty, evidence, and change in dental education: employing evidence-based dentistry in dental education.

Variation in health care, and more particularly in dental care, was recently chronicled in a Readers Digest investigative report. The conclusions of this report are consistent with sound scientific studies conducted in various areas of health care, including dental care, which demonstrate substantial variation in the care provided to patients. This variation in care parallels the certainty with which clinicians and faculty members often articulate strongly held, but very different opinions. Using a case-based dental scenario, we present systematic evidence-based methods for accessing dental health care information, evaluating this information for validity and importance, and using this information to make informed curricular and clinical decisions. We also discuss barriers inhibiting these systematic approaches to evidence-based clinical decision making and methods for effectively promoting behavior change in health care professionals.

Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice.

BACKGROUND: Retrospective and correlation studies suggest that early-onset periodontal disease may be due to a deficiency in phagocyte function, a pathogenic oral biofilm, and/or dysregulated gingival cytokine expression. Increased susceptibility to periodontal disease is therefore thought to result from multiple risk factors. METHODS: We tested this hypothesis prospectively using P/E-selectin adhesion molecule deficient mice that mimic the human syndrome leukocyte adhesion deficiency II. RESULTS: Our studies demonstrate that, in comparison to wild type animals, P/E-/- mice exhibit: spontaneous, early onset alveolar bone loss which is significant by 6 weeks of age; a 10-fold elevation in bacterial colonization of their oral cavities; and elevated gingival tissue levels of the bone resorptive cytokine IL-1alpha. Alveolar bone loss is completely prevented by prophylactic antibiotic therapy. CONCLUSIONS: These experiments provide the first prospective evidence for the multiple risk factor hypothesis of periodontal disease, and validate the first animal model for early onset periodontitis in which both the microbiota and host response can be systematically manipulated. P/E-/- animals should be useful in testing the virulence of putative periodontal pathogens, in determining the role of host resistance factors in periodontitis, in exploring the proposed relationship(s) between infection mediated alveolar bone loss and systemic health disorders, and exploring their genetic relationships.

An unusual pathway of excitation energy deactivation in carotenoids: singlet-to-triplet conversion on an ultrafast timescale in a photosynthetic antenna.

Carotenoids are important biomolecules that are ubiquitous in nature and find widespread application in medicine. In photosynthesis, they have a large role in light harvesting (LH) and photoprotection. They exert their LH function by donating their excited singlet state to nearby (bacterio)chlorophyll molecules. In photosynthetic bacteria, the efficiency of this energy transfer process can be as low as 30%. Here, we present evidence that an unusual pathway of excited state relaxation in carotenoids underlies this poor LH function, by which carotenoid triplet states are generated directly from carotenoid singlet states. This pathway, operative on a femtosecond and picosecond timescale, involves an intermediate state, which we identify as a new, hitherto uncharacterized carotenoid singlet excited state. In LH complex-bound carotenoids, this state is the precursor on the reaction pathway to the triplet state, whereas in extracted carotenoids in solution, this state returns to the singlet ground state without forming any triplets. We discuss the possible identity of this excited state and argue that fission of the singlet state into a pair of triplet states on individual carotenoid molecules constitutes the mechanism by which the triplets are generated. This is, to our knowledge, the first ever direct observation of a singlet-to-triplet conversion process on an ultrafast timescale in a photosynthetic antenna.

Bacterial photosynthesis in surface waters of the open ocean.

The oxidation of the global ocean by cyanobacterial oxygenic photosynthesis, about 2,100 Myr ago, is presumed to have limited anoxygenic bacterial photosynthesis to oceanic regions that are both anoxic and illuminated. The discovery of oxygen-requiring photosynthetic bacteria about 20 years ago changed this notion, indicating that anoxygenic bacterial photosynthesis could persist under oxidizing conditions. However, the distribution of aerobic photosynthetic bacteria in the world oceans, their photosynthetic competence and their relationship to oxygenic photoautotrophs on global scales are unknown. Here we report the first biophysical evidence demonstrating that aerobic bacterial photosynthesis is widespread in tropical surface waters of the eastern Pacific Ocean and in temperate coastal waters of the northwestern Atlantic. Our results indicate that these organisms account for 2-5% of the photosynthetic electron transport in the upper ocean.

Reevaluation of the electrophoretic migration behavior of soluble globular proteins in the native and detergent-denatured states in polyacrylamide gels.

Although sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis is widely used for estimating molecular masses of proteins, considerable uncertainty still exists both about the structure of SDS-protein complexes and about their mechanism of electrophoretic migration. In this study, soluble globular proteins, with masses of 14-200 kDa, were heat-denatured in the presence of SDS and their relative total molecular volume and net charge were estimated from Ferguson plots of electrophoretic mobility vs acrylamide concentration. Native globular protein served as standards for overall molecular size and effective radii. Results revealed at least two independent electrophoretic migration mechanisms for the SDS-protein complexes: (i) for proteins in the 14-65 kDa range at <15% acrylamide, linear Ferguson plots suggested that they migrated ideally and that their effective radii could be estimated in this manner: (ii) concave plots at higher gel concentrations, and for complexes derived from larger proteins, indicated that migration in these cases could be described by reptation theory. Migration of the large proteins at lower gel concentrations and small proteins at higher gel concentrations was not well described by either theory, representing intermediate behavior not described by these mechanisms. These data support models in which all but the smallest SDS-protein complexes adopt a necklace-like structure in which spherical micelles are distributed along the unfolded polypeptide chain. Possible relations to recent alternative models of gel electrophoresis are also discussed.