Engineered Fibrillar Microenvironments With Controllable Architecture and Mechanics for Studying Cellular Stiffness Sensing

Abstract

The mechanical properties of the extracellular matrix (ECM) have emerged as fundamental players in numerous basic cellular functions such as spreading, migration, proliferation and differentiation, thus impacting many biological processes including embryonic development, adult tissue homeostasis, and disease pathogenesis such as fibrosis and cancer [1,2,3]. Synthetic matrices have been crucial to studying the effect of mechanics on cell behavior, as they allow for precise control of mechanical properties over a wide stiffness range, unachievable in vivo or in many naturally derived material systems. Seminal work employing polyacrylamide hydrogels of varying stiffness to direct the differentiation of human mesenchymal stem cells concluded that the bulk modulus, a measure of the material’s resistance to uniform deformation, is a defining parameter influencing cell function [4]. While much current effort aims to shed light on the molecular mechanisms governing stiffness sensing, existing knowledge is limited by the dissimilarity between the simple hydrogel surfaces employed in these studies and the topographically and mechanically more complex ECM cells routinely reside within in vivo. In contrast to the flat expanse of cell adhesive ligand and linear elastic, continuum behavior of typical gel systems, within the body, cell-scale mechanics and ligand availability are entwined, as both are defined by the presence and organization of the proteins that compose the surrounding ECM. The structure of native ECMs vary but largely are fibrillar, given that collagen comprises approximately 25% of the human body by mass. Thus, there remains a significant need for engineered fibrillar materials that afford precise and independent control of architectural features and resulting mechanical properties for application in cell biology. In this work, we establish a novel material system towards this end.