EAPSI: Mechanosensitive hydrogels to measure the forces cells exert on their environment

Tentori Augusto M, Berkeley CA

Investigators

Abstract

Cells in solid tissue are surrounded by the extra cellular matrix (ECM), a complex assortment of proteins and other biomolecules. The ECM provides chemical and mechanical signals to guide cell behavior, however, it is still not entirely understood how cells sense and respond to these signals. Progress in this area has been limited by a lack of tools to measure the mechanical forces cells exert in biologically relevant conditions. Therefore, in collaboration with Dr. Jong-Man Kim at Hanyang University in Seoul, South Korea, this research aims to create an analytical platform to allow researchers to directly measure the cell-generated forces in three dimensional cell culture systems. Dr. Jong-Man Kim and his research group are experts in the synthesis of polydiacetylene (PDA) vesicles that exhibit a mechanosensitive fluorescence response. The development of better research tools to measure these forces would enable a better understanding of processes such as tumor invasion in cancer and cellular differentiation during development, as well as lead to advances in areas such as tissue engineering for regenerative medicine. Cells bind directly to ECM proteins with integrins, forming cell-matrix adhesions which mediate signaling between the cell and local microenvironment. 3D models of tissue culture consist of gel structures in which cells may be directly suspended in, better simulating the in vivo microenvironment compared to surface 2D culture systems. These PDA vesicles can be chemically modified to display protein motifs native to the ECM, such as the RGD (Arg-Gly-Asp) motif, enabling cells to form adhesions with the vesicles. Thus, this research aims to fabricate and characterize 3D scaffolds containing PDA-RGD vesicles, with the goal of enabling direct observation of cell-matrix forces. This NSF EAPSI award is funded in collaboration with the National Research Foundation of Korea.