Mechanics and Properties of Biopolymer Networks and Cells

Abstract

Many naturally derived biomaterials have porous structures. These porous structures are closely related to the mechanical performance of the biomaterial, such as the stability and stiffness. In the meantime, these porous structures are also of great biological importance. They serve as essential physical scaffolds to lodge the cells, and they provide various mechanical cues that can affect cell behaviors such as attachment, speading, and differentiation. In this thesis, we explore the aforementioned two aspects of microstructure by using several porous materials as examples. We first explore the correlation between the structure network and the mechanical property of fibrin with modulation by Zn2+. We find that as the concentration of Zn2+ increases, the diameter of a fibrin fiber becomes thicker, whereas the mesh size of the fibrin network becomes larger. Moreover, bulk rheological measurements show that network shear modulus decreases with the increase of Zn2+ concentration. We then adapt the semi-flexible polymer model to bridge the network topology and mechanical property, and we further predict that each fiber is a loosely coupled bundle of protofibrils. Next, we investigate the influence of hydrogel microstructure on the cell behavior. By culture cell on hydrogels with different microstructure and same stiffness, we investigate the cell behaviors such as attachment, spreading, and differentiation. We find that cell attachment and proliferation are not obviously affected by varying hydrogel pore size, however, cell spreads bigger and migrates faster on hydrogel with smaller pores. We show that focal adhesion formation and nuclear translocation of Yes-associated protein (YAP) is promoted, indicating the cellular mechanotransduction is modulated by hydrogel microstructure. Then we investigate the effect of surface topography on the cell behavior. By culturing bone marrow-derived stem cell (BMSC) on nanoporous membranes with controlled nanopore size and roughness. We find that increasing the roughness of nanoporous surface has no noticeable effect on cell attachment, and only slightly decreases cell spreading areas and inhibits osteogenic differentiation. However, BMSCs cultured on membranes with larger nanopores have significantly fewer attached cells and larger spreading areas. Moreover, these cells cultured on larger nanopores undergo enhanced osteogenic differentiation.