Extracellular Matrix Mechanics and Implications for Cellular Mechanosensing
The cells and tissues in our body owe their shape and mechanical strength to internal frameworks of protein biopolymers. Cells are supported by a composite network of cytoskeletal filaments, while tissues are supported by an extracellular matrix that is composed of fibrous proteins such as collagen. Mechanical measurements on whole cells and tissues have demonstrated intriguing material properties, including strain-stiffening and non-equilibrium behavior that originates from active stress generation by the cellular cytoskeleton. The nonlinear (strain-stiffening) response to external forces is thought to protect cells and tissues from mechanical damage. Experimental and theoretical studies of such simplified single-component biopolymer networks have shown that the nonlinear elasticity of cells and tissues stems from the physical properties of these polymers. However, existing theoretical models of biopolymer networks treat the filaments as simple elastic beams or as semiflexible polymers, ignoring the internal molecular packing structure. I will present experimental evidence that the molecular packing structure can in fact have important consequences for the macroscopic mechanical properties of biopolymer networks. To illustrate the point, I will contrast the mechanical properties of two extracellular matrix polymers: collagen and fibrin, which form networks with near-identical network architecture and filament size. Nevertheless, collagen networks behave as networks of athermal (stiff) rods, whereas fibrin networks exhibit entropic elasticity and elastomeric properties. I will review our recent efforts to link this behavior to the molecular scale, based on small angle X-ray scattering and optical tweezer measurements.
Bio
Gijsje Koenderink (1974) studied Chemistry at Utrecht University in the Netherlands (1998) and obtained her PhD at the same university in 2003 in the area of colloid and physical chemistry. During her postdoc at the VU University Amsterdam (2003-2004) and Harvard University (2004-2006) she redirected her research towards cellular biophysics. In 2006, she started her group Biological Soft Matter at the FOM Institute AMOLF in Amsterdam. She became an affiliated professor at the VU University in 2011 and is head of the Systems Biophysics Department at AMOLF since 2014. Her research focuses on the physical principles that underlie the self-organization and dynamics of living cells. Cellular life critically relies on dynamic processes such as cell division, growth, and migration. These processes are powered by the cytoskeleton, which self-organizes into a variety of complex structures and uses molecular motors to actively deform itself. The Koenderink group uses quantitative physics-based methods based on advanced microscopy and mechanical probing to elucidate how cell behaviour at the mesoscale is driven by interactions at the molecular scale. In addition, her group studies how cell shape and mechanics is influenced by mechanochemical interactions with the extracellular matrix. By performing quantitative experiments on well-controlled minimal cell and tissue models, this research provides a sound physical basis for understanding the role of the cytoskeleton in cellular functions. At the same time, the work addresses questions of interest to a broad physics community since the cytoskeleton is a paradigmatic example of an emerging new class of soft matter referred to as “active soft matter”. Gijsje Koenderink is the recipient of a VIDI grant from NWO (2008) and an ERC Starting Grant (2013).