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Collagen matrix remodeling by fibroblasts monitored by interstitial flow metrology


The Starling principle has been invoked during a century to describe the balance between interstitial flows as pressure and osmotic flows. More recently, our understanding of the lymphatic system has dramatically changed our view on interstitial flows as a balance between (i) blood pressure permeation and (ii) lymphatic drainage. The extracellular matrix (ECM) acts as a microfluidic network that controls the amplitude of interstitial flows. Deregulation of this homeostasis is tightly coupled to a broad range of basic biological mechanisms, including diferenciation, proliferation and migration. In this context, microphysiological systems stand out as dedicated platforms to study the regulation of interstitial flows by the ECM. So far, however, control and measurement of these minute flows has remained an unmet challenge. In this work, we present a technology to directly induce and measure flow rates in commonly used ECM. Its working principle consists of an hydrodynamic actuation system to control pressure in a microchannel embedded into an ECM. Instead of using a flow meter to monitor the resulting flow, we enclose the device with an air cavity, which is compressed or expanded due to the interstitial fluid volume exchanges. A MEMS-based pressure sensor enables the direct determination of the cavity pressure and hence of the intertitial fluid flow rate. We then demonstrate how stromal cells (eg. fibroblast) modulate hydrodynamic and mechanical properties of the ECM. Our results are supported by an original poroelastic model of the ECM. Altogether, our unique tool provides novel insights on intersitial flows and their regulation by cells.
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Dates and versions

hal-03821244 , version 1 (21-10-2022)


  • HAL Id : hal-03821244 , version 1


Jean Cacheux, Aurélien Bancaud, Jose Ordonez-Miranda, Laurent Jalabert, Yukiko T Matsunaga. Collagen matrix remodeling by fibroblasts monitored by interstitial flow metrology. Microphysiological systems: from organoids to organ-on-chip, Apr 2020, Cargèse, France. ⟨hal-03821244⟩
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