CELLMECH · Molecular-Physical Basis of Cell-Biomaterial Mechanical Coupling

Molecular-Physical Basis of Cell-Biomaterial Mechanical Coupling

Our main goal is to study the molecular-physical basis of cell mechanosensing. The realization that cells are as sensitive to the mechanical properties of their environment as much as to its chemical composition is relatively new and the basis for this phenomenon is still unclear. One of the major questions in the lab is the role of mechanical communication mediated by deformations in soft biomaterials in synchronized cell behavior and the ability to manipulate it for regenerative medicine applications. Using a unique combination of high resolution optical microscopy, single molecule imaging, protein-engineered biomaterials design and theoretical modeling, we would like to address several open key questions in the field. These include the ability of elastic interactions mediated by mechanical deformations in the matrix to act as a long range interaction force between biological cells, the molecular mechanism underlying the ability of cells to sense and respond to the mechanical properties of their environment and the significance of the dynamical mechanical properties of the matrix in directing cell behavior and mechanical communication. We established two primary cultures in the lab to study these questions. Neonatal-derived cardiomyocytes and DRG sensory neurons. We have recently demonstrated mechanical communication between cells directly for the first time, providing evidence for a long-range interaction that induces long-lasting alterations in interacting cells. We show that an isolated cardiac cell can be trained to beat at a given frequency by mechanically stimulating the underlying substrate. Deformations were induced using an oscillatory mechanical probe that mimics the deformations generated by a beating neighboring cardiac cell. Stimulation at frequencies above a specific threshold, results in a bursting behavior. Surprisingly, different than electrical field stimulation, the probe-induced beating rate is maintained by the cell for over an hour after the stimulation was stopped, implying that long-term modifications occurred within the cell. We also show that these mechanically-induced long-term alterations provide a mechanism for cells that communicate mechanically to be less variable in their electromechanical delay. Mechanical coupling between cells therefore ensures that the final outcome of action potential pacing is synchronized beating. We further show that the contractile machinery is essential for mechanical communication. In addition, we have recently designed and expressed a unique protein-engineered biomaterial that was tailored to promote mechanical communication between cardiac cells. My group website is: cellmech.net.technion.ac.il

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