Main research interests
The ability of cells to sense their mechanical surroundings is essential to many physiological processes, including cell migration, proliferation, differentiation, and apoptosis. However, despite recent discoveries of many mechanosensitive proteins, their role in guidance of cell behaviour largely remains obscure. Indeed, while force spectroscopy methods have greatly improved our understanding of the mechanosensing mechanisms of such proteins, much less is known about how their force-dependent response is integrated at the mesoscale level, ultimately directing cell behaviour.
Our long-term interest is to study the molecular pathways involved in the integration of extracellular and intracellular mechanical forces into the cell signalling network, as they play a major role in the processes of embryonic development, wound healing, and human-related diseases, such as cancer.
To this end, we use a combination of both experimental and theoretical methods to approach the problem from different angles to gain deeper insights into the underlying molecular mechanisms. We have mastered and applied in the research such experimental methods as optical and magnetic tweezers, atomic force and confocal microscopy. Also, we have been actively utilizing the chemical kinetics theory, Brownian dynamics simulations, statistical physics as well as polymer field theory for understanding of mechanobiological processes taking place in living cells.
Major Research Achievements
- Development of a general theoretical framework and the fastest (in the world) computational algorithm capable of predicting the conformation of DNA and changes in its interaction with DNA-binding proteins under mechanical and geometric constraints at the single-molecule and mesoscale levels.
- Development of a numerical algorithm for predicting the mesoscale organization of the cell genome based on the physicochemical properties and architecture of individual nucleoprotein complexes. Discovery of the piezoelectric behavior of the cell nucleus and its potential role in nuclear organization.
- Discovery of the role of formins and myosin IIA motor proteins in the regulation of the mechanosensory function of filopodia.
- Discovery of force-induced Ca2+ signaling mediated by L-type Ca2+ channels in filopodia, which results in activation of Ca2+-sensitive calpain protease involved in the regulation of cell adhesion complexes.
- Discovery of multistable mechanosensitive behaviour of cell adhesion and the potential role of the elastic properties of cytoskeletal adapter proteins in its regulation.