Viscoelastic and interfacial mechanisms of cell-matrix interactions in dynamic environments.

摘要

This work addresses the mechanisms underlying the interfacial interactions between cells and a surrounding biopolymer matrix. During their growth process, cells are surrounded by an Extracellular Matrix (ECM) that plays a critical role in cell development, since it provides physical support, regulates cell attachment and migration, and transports nutrients and biochemical signaling compounds. The morphology, lineage specification, and phenotypic expression are all affected by the surrounding environment.;The traditional method of cell growth and manipulation in a laboratory employs 2-D geometries where cells are attached to a substrate. This method has several limitations and does not emulate the in vivo environment. A 3-D ECM provided by a polymeric network can provide better cellular support and maintain the metabolism and functionality of surviving cells. The mechanical characteristics, chemical components and surface morphology of a 3-D polymer cell matrix can be tailored to address specific requirements for cell growth and development. When cells are embedded in a biocompatible synthetic ECM, the architecture of the biomaterial could transduce the physical stimuli exerted on the matrix in the form of compression, tension or shear. Compared to regulating the cell development process via biochemical pathways, using mechanical stimuli would be less complicated in application. The integrated mechanical stimuli is more controllable overall, the applied force can be precise, and the response is fast. Once the mechanisms of how physical stimuli contribute to the differential expression of cell phenotypes and what amount is needed for certain lineage specification, one can design programmable physical inputs during cell growth.;For the purpose of acquiring a thorough understanding of the impact of mechanical stimuli transduced to cells by an ECM, a closer examination of the cell-matrix interfacial interactions can provide valuable insights. We have developed both experimental and computational tools to study such mechanisms. A systematic investigation of how the embedment of cells influences the structure and rheology of biocompatible polymeric matrices in a dynamic environment is conducted to decipher the effect of shear-induced changes in the microstructure on physical properties such as viscosity, elastic/loss moduli, and gelation temperature.