Edward Teller Professor and Chair of Biomedical Engineering University of California, Davis Davis, California, United States
Introduction: : Microfluidic technologies offer a wide range of possibilities to understand biological phenomena. While our lab has used them to re-create 3D microenvironments that mimic human tissues (microphysiological systems or “organ-on-a-chip” technology) including the microcirculation, bone marrow, and tumor microenvironments, we have also been able to leverage microfluidics to control the biophysical microenvironment to address fundamental questions in mechanobiology.
Materials and
Methods: : For example, we demonstrated that physiological levels of interstitial flow (~ 1 micron/sec) can effectively eliminate spatial gradients in the interstitial space, but this same level of flow stimulates angiogenesis in the direction of flow in the presence of VEGF. We demonstrated a similar phenomenon in breast cancer organoids in which K14+ leader cells migrate to the leading edge and initiate DDR2-dependent migration in response to interstitial flow, again in the direction of interstitial flow. More recently we used a similar microfluidic device to demonstrate that the transport of extracellular vesicles in the interstitium under physiological levels of interstitial flow is controlled by convection and binding to the matrix (diffusion is negligible). Finally, we are using a simple microfluidic device design to control fluid shear at a functionalized surface to isolate rare and specific immune cells in the peripheral circulation.
Results, Conclusions, and Discussions:: These studies use an array of simple microfluidic designs to control fluid flow and thus the mechanical microenvironment and demonstrate how very low levels of mechanical force induced by physiological interstitial flow can have profound biological impact. This talk will provide an overview of these studies highlighting how simple microfluidic designs can be used to interrogate impactful questions in mechanobiology.
