| 研究開始時の研究の概要 |
The purpose of the proposed research is to analyze how integrity of a MV (Micro-Vess el) can be maintained or can dysfunction and lead to adverse modulation in permeabil ity. To do so, we aim to use microfluidics and develop an all-in-one solution to observe, stimulate, and characterize perfusable 3D MV in vitro in space and time.
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| 研究実績の概要 |
Firstly, we went further instrumenting the device with a pressure sensor embedded into an air cavity. We also have developped an 1D analytical model to predict the diffusion of the pressure gradient according to the permeability and elasticity of collagen gel. This unique approach allowed us to show a drop in the permeability and enhanced strain-stiffening of native collagen gels under compression vs. tension, both effects being essentially lost after chemical cross-linking. Further, we report the control of the permeability of native collagen gels using sinusoidal fluid injection, an effect explained by the asymmetric response in tension and compression.
Secondly, we compare the transport of macromolecules through endothelial tissues at mechanical rest or with intraluminal pressure, and correlate these data with electron microscopy of endothelial junctions. Upon application of an intraluminal pressure of 100 Pa, we demonstrate that the flow through the tissue increases by 2.35 times. This increase is associated with a 25% expansion of microvessel diameter, which leads to tissue remodeling and thinning of the paracellular junctions. We recapitulate these data with the deformable monopore model, in which the increase in paracellular transport is explained by the augmentation of the diffusion rate across thinned junctions under mechanical stress.
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