Seminar: Stimuli responsive mechanical systems: from biological cells to magneto-active hydrogels
Abstract: Critically important biological phenomena in health and disease, such as wound healing, cancer metastasis, and embryonic development, are governed by collective cell migration. This highly complex process depends not only on cellular features, but also on different stimuli from the local cell environment. Cell migration is promoted by the combination of physico-chemical cues, including the mechanical properties of the extracellular matrix (ECM). Stiffness gradients within ECM have recently been demonstrated to result into preferred directions of cell migration. To reproduce such processes, in vitro experiments commonly use soft polymeric materials as ECM for the biological system studied. The main limitation of these materials to simulate biological phenomena relates to their incapability of responding dynamically during the process, i.e., during wound healing (internal stresses, change in stiffness, etc). In this regard, to potentially overcome such a limitation, soft materials have experienced a significant advance during the last years. Among these materials, stimuli-responsive hydrogels offer great opportunities for novel applications within this field. However, the design of these stimuli-responsive (i.e., magneto-responsive) materials is rather complex as they combine nonlinear mechanical behaviour, rate dependencies, magneto-active responses and solvent diffusion processes. Here, we first evaluate the specific mechanisms driving directed collective cell migration. To this end, we develop a continuum formulation and its finite element (FE) implementation to test different hypotheses on the cause of spatial heterogeneities during cell migration on heterogeneous-stiffness substrates. Then, we move to magneto-active hydrogels and propose a general constitutive and FE framework to couple magnetics, diffusion and nonlinear mechanics. This framework is particularized and implemented for 3D problems. Overall, these works provide a flexible computational framework to design further cellular substrates by using magneto-active hydrogels to simulate mechanical-dynamic processes such as wound healing.