Topological balance of cell distributions in plane monolayers.

Most of normal proliferative epithelia of plants and metazoans are topologically invariant and characterized by similar cell distributions according to the number of cell neighbors (DCNs). Here we study peculiarities of these distributions and explain why the DCN obtained from the location of intercellular boundaries and that based on the Voronoi tessellation with nodes located on cell nuclei may differ from each other. As we demonstrate, special microdomains where four or more intercellular boundaries converge are topologically charged. Using this fact, we deduce a new equation describing the topological balance of the DCNs. The developed theory is applied for a series of microphotographs of non-tumoral epithelial cells of the human cervix (HCerEpiC) to improve the image processing near the edges of microphotographs and reveal the topological invariance of the examined monolayers. Special contact microdomains may be present in epithelia of various natures, however, considering the well-known vertex model of epithelium, we show that such contacts are absent in the usual solid-like state of the model and appear only in the liquid-like cancer state. Also, we discuss a possible biological role of special contacts in context of proliferative epithelium dynamics and tissue morphogenesis.

Topological properties and shape of proliferative and nonproliferative cell monolayers.

During embryonic development, structures with complex geometry can emerge from planar epithelial monolayers; studying these shape transitions is of key importance for revealing the biophysical laws involved in the morphogenesis of biological systems. Here, using the example of normal proliferative monkey kidney (COS) cell monolayers, we investigate global and local topological characteristics of this model system in dependence on its shape. The obtained distributions of cells by their valence demonstrate a difference between the spherical and planar monolayers. In addition, in both spherical and planar monolayers, the probability of observing a pair of neighboring cells with certain valences depends on the topological charge of the pair. The zero topological charge of the cell pair can increase the probability for the cells to be the nearest neighbors. We then test and confirm that analogous relationships take place in a more ordered spherical system with a larger fraction of 6-valent cells, namely, in the nonproliferative epithelium (follicular system) of ascidian species oocytes. However, unlike spherical COS cell monolayers, ascidian monolayers are prone to nonrandom agglomeration of 6-valent cells and have linear topological defects called scars and pleats. The reasons for this difference in morphology are discussed. The morphological peculiarities found are compared with predictions of the widely used vertex model of epithelium.

Packing and trimer-to-dimer protein reconstruction in icosahedral viral shells with a single type of symmetrical structural unit.

Understanding the principles of protein packing and the mechanisms driving morphological transformations in virus shells (capsids) during their maturation can be pivotal for the development of new antiviral strategies. Here, we study how these principles and mechanisms manifest themselves in icosahedral viral capsids assembled from identical symmetric structural units (capsomeres). To rationalize such shells, we model capsomers as symmetrical groups of identical particles interacting with a short-range potential typical of the classic Tammes problem. The capsomere particles are assumed to retain their relative positions on the vertices of planar polygons placed on the spherical shell and to interact only with the particles from other capsomeres. Minimization of the interaction energy enforces equal distances between the nearest particles belonging to neighboring capsomeres and minimizes the number of different local environments. Thus, our model implements the Caspar and Klug quasi-equivalence principle and leads to packings strikingly similar to real capsids. We then study a reconstruction of protein trimers into dimers in a Flavivirus shell during its maturation, connecting the relevant structural changes with the modifications of the electrostatic charges of proteins, wrought by the oxidative switch in the bathing solution that is essential for the process. We highlight the key role of pr peptides in the shell reconstruction and show that the highly ordered arrangement of these subunits in the dimeric state is energetically favored at a low pH level. We also discuss the electrostatic mechanisms controlling the release of pr peptides in the last irreversible step of the maturation process.

Random nature of epithelial cancer cell monolayers.

Although the polygonal shape of epithelial cells has been drawing the attention of scientists for several centuries, only a decade and a half ago it was demonstrated that distributions of polygon types (DOPTs) are similar in proliferative epithelia of many different plant and animal species. In this study, we show that hyper-proliferation of cancer cells disrupts this universal paradigm and results in randomly organized epithelial structures. Examining non-synchronized and synchronized HeLa cervix cells, we suppose that the spread of cell sizes is the main parameter controlling the DOPT in the cancer cell monolayers. To test this hypothesis, we develop a theory of morphologically similar random polygonal packings. By analysing differences between tumoural and normal epithelial cell monolayers, we conclude that the latter have more ordered structures because of their lower proliferation rates and, consequently, more effective relaxation of mechanical stress associated with cell division and growth. To explain the structural features of normal proliferative epithelium, we take into account the spread of cell sizes in the monolayer. The proposed theory also rationalizes some highly ordered unconventional post-mitotic epithelia.

Irreversible and reversible morphological changes in the φ6 capsid and similar viral shells: symmetry and micromechanics.

Understanding the physicochemical processes occurring in viruses during their maturation is of fundamental importance since only mature viruses can infect host cells. Here we consider the irreversible and reversible morphological changes that occur with the dodecahedral φ6 procapsid during the sequential packaging of 3 RNA segments forming the viral genome. It is shown that the dodecahedral shape of all the four observed capsid states is perfectly reproduced by a sphere radially deformed by only two irreducible spherical harmonics with icosahedral symmetry and wave numbers l = 6 and l = 10. The rotation of proteins around the 3-fold axes at the Procapsid → Intermediate 1 irreversible transformation is in fact also well described with the shear field containing only two irreducible harmonics with the same two wave numbers. The high stability of the Intermediate 1 state is discussed and the shapes of the Intermediate 2 state and Capsid (reversibly transforming back to the Intermediate 1 state) are shown to be mainly due to the isotropic pressure that the encapsidated RNA segments exert on the shell walls. The hidden symmetry of the capsid and the physicochemical features of the in vitro genome extraction from the viral shell are also elucidated.

Carbon nanotube sorting due to commensurate molecular wrapping.

Single-walled carbon nanotubes (SWCNTs) can be sorted by their structural parameters using organic molecules and polymers: some of which, demonstrating a profound affinity only for specific nanotubes, form dense coatings on them. Here, analyzing well-known examples of flavin group molecules and those of 2,4-dichlorophenoxyacetic acid, we show for the first time that successful formation of the considered coatings depends on the ability of molecules to wrap around the SWCNT in a commensurate way. Commensurability provides a decrease in the free energy of the resulting bilayer system and makes the coating much more stable. Concurrently, it strongly relates the nanotube chiral vector with the geometric characteristics of the adhering molecules, which leads to revealed selection rules. If they are not satisfied, the deposition of molecules does not occur or is insignificant. The proposed theory unambiguously explains known experimental results on the formation of spiral wrappings of SWCNTs by flavin group molecules and points out other organic molecules and polymers suitable for effective CNT sorting.

Crystal-like order and defects in metazoan epithelia with spherical geometry.

Since Robert Hooke studied cork cell patterns in 1665, scientists have been puzzled by why cells form such ordered structures. The laws underlying this type of organization are universal, and we study them comparing the living and non-living two-dimensional systems self-organizing at the spherical surface. Such-type physical systems often possess trigonal order with specific elongated defects, scars and pleats, where the 5-valence and 7-valence vertices alternate. In spite of the fact that the same physical and topological rules are involved in the structural organization of biological systems, such topological defects were never reported in epithelia. We have discovered them in the follicular spherical epithelium of ascidians that are emerging models in developmental biology. Surprisingly, the considered defects appear in the epithelium even when the number of cells in it is significantly less than the previously known threshold value. We explain this result by differences in the cell sizes and check our hypothesis considering the self-assembly of different random size particles on the spherical surface. Scars, pleats and other complex defects found in ascidian samples can play an unexpected and decisive role in the permanent renewal and reorganization of epithelia, which forms or lines many tissues and organs in metazoans.

Hidden symmetry of the anomalous bluetongue virus capsid and its role in the infection process.

Clear understanding of the principles that control the arrangement of proteins and their self-assembly into viral shells is very important for the development of antiviral strategies. Here we consider the structural peculiarities and hidden symmetry of the anomalous bluetongue virus (BTV) capsid. Each of its three concentric shells violates the paradigmatic geometrical model of Caspar and Klug, which is otherwise well suited to describe most of the known icosahedral viral shells. As we show, three icosahedral spherical lattices, which are commensurate with each other and possess locally hexagonal (primitive or honeycomb) order, underlie the proteinaceous shells of the BTV capsid. This interpretation of the multishelled envelope allows us to discuss the so-called "symmetry mismatch" between its layers. We also analyze the structural stability of the considered spherical lattices on the basis of the classical theory of spherical packing and relate the proximity of the outer spherical lattice to destabilization with the fact that during infection of the cell VP2 trimers are detached from the surface of the BTV capsid. An electrostatic mechanism that can assist in this detachment is discussed in detail.

Commensurability between protein nanotubes in contractile ejection nanomachines.

Contractile ejection nanomachines being sheath-tube assemblies create an opening in the cell membrane to translocate molecules or ions across it. Here, on the most structurally investigated examples of the bacteriophage T4 tail and pyocin R2, we show that the rearrangement of the sheath structure resulting in its contraction and twist occurs in such a way that the contracted sheath becomes commensurate with the inner tube. This fact dictates the previously unknown simple geometrical relationship between the nanotube symmetries. Using the Frank and van der Merwe classical theory of commensurability, we study an interaction between two protein nanotubes forming such nanomachines and obtain an expression for the corresponding energy, which depends on the tube structures and their mutual arrangement. The appearance of commensurability between the contracted sheath and the inner tube decreases both the interaction energy and the total energy of the system. It improves the nanomachine efficiency, since the energy gain obtained increases the torque of the inner tube piercing the cell membrane.