Capillary micromechanics of cell-encapsulated microgels

Cell behaviors, such as adhesion, proliferation, migration and growth, are closely affected by their _x000D_ surrounding environment [1–5]. For example, cells respond to the elasticity of their substrate by _x000D_ changing their stiffness and morphologies [6–12]; stem cell proliferates into different cell types _x000D_ depending on the material properties of substrates including wettability, surface chemistry and _x000D_ elasticity [5,13–15]. Thus, the cell-material interaction is of great importance in understanding the _x000D_ cell responses to signals within their immediate environments [1,2]._x000D_ Due to its tunable elasticity, microgel is frequently employed to mimic tissues or as synthetic _x000D_ substrates to study cell behavior such as adhesion [9]. Microgels are also extensively used as delivery _x000D_ vehicles in vivo [21], or as scaffolds for 3-D cell culture [22]. For these applications, the interaction _x000D_ between the soft hydrogel materials and cells dictate the fate of delivery vehicles or the cultured _x000D_ cells [21,22]. _x000D_ Among the physical and chemical properties of cell/material interfaces, the mechanics between cell _x000D_ and materials receive wide attention [5–9,15,22,24]. It is shown that kidney epithelial and 3T3 _x000D_ fibroblastic cells can feel and respond to the elasticity of substrates by changes in their reduced _x000D_ spreading and increased motility [8]. Other parameters such as cell type and shape also have more _x000D_ pronounced effect on cell stiffness [6]. These correlations enrich our understanding the interaction _x000D_ between cell behavior and the mechanical properties of their adhesive substrates. However, most of _x000D_ the results are obtained in substrates of 2-D geometry while neglecting the possible influence from _x000D_ fluids in the surroundings [25], which is present in most biological systems. Recent advance of _x000D_ microfluidics enables the encapsulation of cells in 3-D microgels with well-defined physiochemical _x000D_ properties. Moreover, a recently developed technique Capillary Micromechanics allows the _x000D_ comprehensive characterization of mechanical properties of microgels at single particle level [26,27]. _x000D_ Thus, Capillary Micromechanics is promising platform to investigate cell response in well-defined _x000D_ microgels with surrounding shearing flow. _x000D_ _x000D_ In this work, we encapsulate single cell in a hydrogel microparticle with different stiffness. By using _x000D_ Capillary Micromechanics, we monitor the subsequent development of the cells and correlate their _x000D_ development with the stiffness of the hydrogel matrices. Moreover, the cell proliferation in response _x000D_ to different pressure exerted by surrounding fluids, which is present in vivo, is also investigated. We IAS Program on Frontiers of Soft Matter Physics: from Non-equilibrium Dynamics to Active Matter | 2-29 Jan 2014_x000D_ demonstrate our approach can be used for studying cell growth in well-controlled environment _x000D_ systematically. Our understandings can provide important guideline when designing hydrogel _x000D_ carriers for biological materials, such as cells and embryos.