Artem Efremov Lab

Discovery of multistable mechanosensitive behaviour of cell adhesion and the potential role of the elastic properties of cytoskeletal adapter proteins in its regulation

• Date: 2022
• Institution: Shenzhen Bay Laboratory (China), Mechanobiology Institute (Singapore)
• Authors: Artem Efremov, Ladislav Hovan, Jie Yan
• Aim of study: Mechanosensory perception of living cells is important for regulation of many physiological processes, including cell migration, proliferation, differentiation and apoptosis. Furthermore, it plays a central role in development of various pathological conditions such as fibrosis, cancer, and cardiovascular diseases. Recently, it was shown that the elastic characteristics of cytoskeletal adapter proteins, such as talin, can have a strong influence on the force mechanotransduction and composition of adhesion protein complexes in living cells. Yet, previous theoretical studies predict that cell adhesion should have low sensitivity to this key factor, suggesting a lack of understanding of the underlying molecular mechanisms. To solve this problem, we developed and experimen-tally tested a cell adhesion model that includes a physically realistic description of the force-dependent behaviour of talin and local substrate deformations at cell adhesion sites in order to investigate how the interplay between these two factors affects mechanosensitive cell behaviour.

Major results: The developed semi-analytical approach based on consideration of the long-term behaviour of molecular links between the cell cytoskeleton and extracellular matrix, has made it possible to accurately fit previously published experimental data and construct a simple geometric interpretation of the dynamic behaviour of the cell adhesion complexes. It revealed that the latter undergoes a series of bifurcations that result in a strong sensitivity of cell behaviour to the elastic properties of adapter proteins, such as talin, and the contractile activity of myosin II motors, thus giving new insights into the potential biological functions of these proteins. In addition, the developed model predicted the existence of a molecular pathway responsible for the regulation of the number of contractile myosin II motors in response to changes in the fibronectin density, which was experimentally confirmed in our study.

Contribution to the research field:Although the article describing the above results has not yet been published, we expect that it will have a substantial impact on understanding the role of the elastic properties of adapter proteins and their nonlinear force-response in shaping the mechanosensitive behaviour of cell adhesion. Furthermore, the multistable behaviour of cell adhesion revealed in our study, provides new important insights into the shock-absorbing function of adapter proteins and their potential synergistic cooperation in the formation of cell adhesion complexes.