Survival-Associated Cellular Response Maintained in Pancreatic Ductal Adenocarcinoma (PDAC) Switched Between Soft and Stiff 3D Microgel Culture.

Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of all pancreatic cancer cases. Five-year survival rates have remained below 12% since the 1970s, in part due to the difficulty in detection prior to metastasis (migration and invasion into neighboring organs and glands). Mechanical memory is a concept that has emerged over the past decade that may provide a path toward understanding how invading PDAC cells "remember" the mechanical properties of their diseased ("stiff", elastic modulus, E ≈ 10 kPa) microenvironment even while invading a healthy ("soft", E ≈ 1 kPa) microenvironment. Here, we investigated the role of mechanical priming by culturing a dilute suspension of PDAC (FG) cells within a 3D, rheologically tunable microgel platform from hydrogels with tunable mechanical properties. We conducted a suite of acute (short-term) priming studies where we cultured PDAC cells in either a soft (E ≈ 1 kPa) or stiff (E ≈ 10 kPa) environment for 6 h, then removed and placed them into a new soft or stiff 3D environment for another 18 h. Following these steps, we conducted RNA-seq analyses to quantify gene expression. Initial priming in the 3D culture showed persistent gene expression for the duration of the study, regardless of the subsequent environments (stiff or soft). Stiff 3D culture was associated with the downregulation of tumor suppressors (LATS1, BCAR3, CDKN2C), as well as the upregulation of cancer-associated genes (RAC3). Immunofluorescence staining (BCAR3, RAC3) further supported the persistence of this cellular response, with BCAR3 upregulated in soft culture and RAC3 upregulated in stiff-primed culture. Stiff-primed genes were stratified against patient data found in The Cancer Genome Atlas (TCGA). Upregulated genes in stiff-primed 3D culture were associated with decreased survival in patient data, suggesting a link between patient survival and mechanical priming.

Extracellular Optogenetics at the Interface of Synthetic Biology and Materials Science.

We review fundamental mechanisms and applications of OptoGels: hydrogels with light-programmable properties endowed by photoswitchable proteins ("optoproteins") found in nature. Light, as the primary source of energy on earth, has driven evolution to develop highly-tuned functionalities, such as phototropism and circadian entrainment. These functions are mediated through a growing family of optoproteins that respond to the entire visible spectrum ranging from ultraviolet to infrared by changing their structure to transmit signals inside of cells. In a recent series of articles, engineers and biochemists have incorporated optoproteins into a variety of extracellular systems, endowing them with photocontrollability. While other routes exist for dynamically controlling material properties, light-sensitive proteins have several distinct advantages, including precise spatiotemporal control, reversibility, substrate selectivity, as well as biodegradability and biocompatibility. Available conjugation chemistries endow OptoGels with a combinatorially large design space determined by the set of optoproteins and polymer networks. These combinations result in a variety of tunable material properties. Despite their potential, relatively little of the OptoGel design space has been explored. Here, we aim to summarize innovations in this emerging field and highlight potential future applications of these next generation materials. OptoGels show great promise in applications ranging from mechanobiology, to 3D cell and organoid engineering, and programmable cell eluting materials.

Correction: Aqueous surface gels as low friction interfaces to mitigate implant-associated inflammation.

Correction for 'Aqueous surface gels as low friction interfaces to mitigate implant-associated inflammation' by Allison L. Chau et al., J. Mater. Chem. B, 2020, 8, 6782-6791, DOI: .

Poroelasticity of highly confined hydrogel films measured with a surface forces apparatus.

The influence of poroelasticity on the contact mechanics of thin polyacrylamide films was investigated with a surface forces apparatus (SFA). A model based on a thin film approximation described compression forces for hydrated gels; polymer scaling theory explained the effects of gel dehydration. The results demonstrate that fluid flow dictates the apparent stiffness of highly confined poroelastic films.

Aqueous surface gels as low friction interfaces to mitigate implant-associated inflammation.

Aqueous surface gels are fragile yet resilient biopolymer-based networks capable of sustaining extremely low friction coefficients despite tribologically-challenging environments. These superficial networks are ubiquitous in natural sliding interfaces and protect mechanosensitive cells from excessive contact pressures and frictional shear stresses from cell-fluid, cell-cell, or cell-solid interactions. Understanding these complex lubrication mechanisms may aid in the development of materials-based strategies for increasing biocompatibility in medical devices and implants. Equally as important is characterizing the interplay between soft and passive yet mobile implant materials and cellular reactions in response to direct contact and frictional shear stresses. Physically interrogating living biological systems without rupturing them in the process is nontrivial. To this end, custom biotribometers have been designed to precisely modulate contact pressures against living human telomerase-immortalized corneal epithelial (hTCEpi) cell layers using soft polyacrylamide membrane probes. Reverse-transcription quantitative polymerase chain-reaction (RT-qPCR) indicated that increased duration and, to a much greater extent, the magnitude of frictional shear stress lead to increased production of pro-inflammatory (IL-1ß, IL-6, MMP9) and pro-apoptotic (DDIT3, FAS) genes, which in clinical studies are linked to pathological pain. The hierarchical structure often found in biological systems has also been investigated through the fabrication of high-water content (polyacrylamide) hydrogels through free-radical polymerization inhibition. Nanoindentation experiments and friction coefficient measurements indicate that these "gradient surface gels" reduce contact pressures and frictional shear stresses at the surface of the material while still maintaining stiffness within the bulk. Reducing frictional shear stresses through informed materials and surface design may concomitantly increase lubricity and quiet the immune response, and thus provide bio-inspired routes to improve patient outcomes and quality of life.