BiFCCM · Bi-directional Force Communication on Cell-Matrix

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bi-directional mechanical exchange is crucial for many cell functions, is remains poorly understood, mostly since the majority of ECMs, both natural and synthetic, are difficult to control or lack biological relevance. A new synthetic polyisocyanide (PIC) gel is the first material that is an excellent mimic of the ECM (porous network architecture and nonlinear mechanics, including stiffening) and can independently tailor mechanical and biological properties. The gel is developed at Radboud University Nijmegen, where I finished my PhD. In this action, I want to study how forces from the cell or the ECM change the mechanical properties of the matrix and, more importantly, how this change affects biological functions. To this end, I will combine the unique, highly tunable PIC gels as synthetic ECM and study the matrix and cell behavior using advanced microscopic imaging techniques and spatial proteomics. Through PIC functionalization, I can tailor the size and number of focal adhesions (FAs), i.e. the protein complexes that link cells to the ECM. The forces generated by cells will be quantified both on cellular and single FA level by traction force microscope (TFM) and molecular tension sensor-based FRET. In addition, proteomic analysis will be performed to evaluate the effect of gels with different mechanical properties in the proteome. These results will have a high impact for understanding how cells interact with matrix through forces. Beyond my knowledge in biomaterials, I will gain new expertise in super-resolution microscope and mechanobiology at KU Leuven. This project highly matches the mission of the Marie Skłodowska-Curie Individual Fellowships to achieve two-way knowledge transfer and to promote my future career prospects.