Cell membrane uptake of bacteria, virions and anorganic particles controlled by membrane mechanics and topology

The configuration and shape changes of membranes are in general correlated with many important biological systems and processes such as membrane encapsulation of nanoparticles (NP), bacteria and virions. The understanding of the interplay between the membrane elastic, topological and electrostatic properties in the process of encapsulation of NPs by the cell membrane is relevant to cellular drug uptake, transmembrane transport of extracellular vesicles, viral budding and phagocytosis, enabling immune cells to destroy foreign elements and clear dead cells and debris. The mechanism of intracellular entry of SARS-CoV-2 is lately also receiving a considerable attention. New theoretical approaches of mechanics and physics in modelling of the cell shape changes influenced by attached, intercalated or encapsulated inorganic NPs, bacteria and virions will be developed or elaborated in this project. These new theoretical approaches will take into account the active forces of the cell cytoskeleton, the anisotropic membrane mechanical properties and topological defects (TDs), which are favourable points for membrane interactions with NPs and highly-curved parts of nanoparticles-decorated surfaces (NPSs). We aim to develop new theoretical models for the uptake of bacteria, virions and NPs by the cell membrane and the models for the adhesion of cells to nanoparticles-decorated surfaces (NPSs), controlled by membrane mechanics and topology. Moreover, the corresponding novel computer programs for numerical modelling and Monte Carlo (MC) simulations of the shape changes and the topology of cell membranes (in contact with NPs or NPSs) will be developed, comprising the main goal of this project proposal. The ordering of anisotropic membrane constituents and embedded/attached NPs does not solely depend on the local mean curvature, but also on the local membrane curvature deviator. So far, only the local mean curvature has been considered as the main parameter in the models of membrane mechanics and in the corresponding numerical and simulations tools. This proposal is one of the first efforts to take into account the membrane curvature deviator and fill this existing gap. The specific means to achieve this goal is the development of new advanced models for the mechanics of anisotropic membranes and ordering of anisotropic membrane constituents. These models can be, in turn, applied to new computational tools in order to quantitatively predict the 3-D closed membrane shapes and ordered membrane domains with topological defects. Therefore, our newly developed numerical and simulations tools to study the 3-D shapes and topological defect distributions on the membranes along with their interactions with NPs and NPSs will be universal. It will also allow for the first time to numerically minimize the free/elastic membrane energy, which can in general be the function of the local mean curvature and the local curvature deviators. The developed numerical and MC simulations tools will be also useful in many other fields of research that deal with 3-D shapes and topologies of thin elastic shells with anisotropic properties. Our numerical calculations and MC simulations will serve as an initial guide for experimental measurements of (a) the changes in the membrane thermodynamic properties such as phase behaviour, (b) the cell topology and membrane mechanical properties associated with the cell/membrane response to spherical and anisotropic NPs, and (c) the response to semiconductor and metal NPSs synthesized in our laboratories. Quartz crystal microbalance with dissipation monitoring, nanoindentation and optical and atomic force microscopy will be used. The evaluation of experimental results on membrane mechanics obtained from supported lipid bilayers and vesicles will be used to further improve and verify the theoretical models together with numerical software and MC simulations.