A Microfluidic Chip for Analysis of Mechanical Forces Generated During Cell Migration
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Microfluidic Chip for Analysis of Mechanical Forces Generated During Cell Migration Xiaoyu Zheng1 Else Frohlich1 , Sean Collignon2 and Xin Zhang1 1 2
Department of Mechanical Engineering, Boston University, Boston, MA 02215, U.S.A Department of Biomedical Engineering, Boston University, Boston, MA 02215, U.S.A
ABSTRACT Vascular smooth muscle cell migration is a microscopic in vivo process where specific cells crawl in order to partake in crucial physiological functions relating to embryonic development, wound healing, and tissue development. Abnormalities of cell migration result in pathologies such as tumor metastasis, angiogenesis, chronic inflammation, and various immune response dysfunctions. The mechanism behind cellular migration and the role of intracellular proteins in the instigation of cell directionality remains poorly understood without effective biomedical device available. The development of microfluidic biochips technologies enable detection, sample preparation and treatment on one single chip. We are reporting the design and fabrication of a novel microfluidic chip for guiding and quantifying cell migrations. The chip featured micropillar arrays imbedded in a multichannel microfluidic chip, where cell migration can be guided by utilizing the characteristics of laminar flow. Non-blending layers of fluid injected through the multi-channel device simulated a wounded edge across a monolayer of cells by limiting flow of trypsin, a serine protease, to half of the main channel, promoting cell migration in a desired direction. Control over cell directionality allows for the measurement and analysis of mechanical forces generated during cell migration in relation to migratory responses from intracellular protein inhibition. The micro-fluidic chip template was designed and manufactured using photolithography techniques. Polydimethylsiloxane (PDMS) served as the bulk material of the two compromising chip layers (channels and pillars), which were subsequently aligned and adhered to form the device. It was confirmed through both computer simulation and experimentation that this device can effectively hold laminar flows of trypsin and cell media. Thus, this microfluidic device allows the user to simultaneously acquire force data during cell migration and observe migratory patterns to ultimately gain a better understanding of the underlying mechanisms of cell migration and directionality. INTRODUCTION When cells begin to migrate, they exerted forces against substrate to move forward. During these processes, forces are generated by the action of myosin on the cytoskeleton through integrin-extracellular matrix linkages to create traction forces on the substrate. In the present study, microfluidic devices were utilized to fabricate precisely controlled wound edges of cell monolayers for the creation of an on-chip cell migration assay. Combining with cell force measurement based on micro pillar arrays, in this work, a novel microfluidic device has been designed to perform mimicked wounded edges on a mon
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