Lipid signaling affects primary fibroblast collective migration and anchorage in response to stiffness and microtopography
| Autor: | Christopher Solís, Michael A. Mkrtschjan, Kevin J. Kappenman, Long V. Le, Snehal B. Gaikwad, Brenda Russell, Tejal A. Desai, Sagar Dommaraju |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry Context (language use) macromolecular substances Mechanotransduction Cellular Article Rats Sprague-Dawley Focal adhesion 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Animals Phosphorylation Mechanotransduction Fibroblast Focal Adhesions Chemistry Cell Membrane Membrane Proteins Cell migration Cell Biology Lipid signaling Fibroblasts Actin cytoskeleton Lipids Cell biology 030104 developmental biology medicine.anatomical_structure Wound healing 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 233:3672-3683 |
| ISSN: | 0021-9541 |
| DOI: | 10.1002/jcp.26236 |
| Popis: | Cell migration is regulated by several mechanotransduction pathways, which consist of sensing and converting mechanical microenvironmental cues to internal biochemical cellular signals, such as protein phosphorylation and lipid signaling. While there has been significant progress in understanding protein changes in the context of mechanotransduction, lipid signaling is more difficult to investigate. In this study, physical cues of stiffness (10 kPa, 100 kPa, 400 kPa, and glass), and microrod or micropost topography were manipulated in order to reprogram primary fibroblasts and assess the effects of lipid signaling on the actin cytoskeleton. In an in vitro wound closure assay, primary cardiac fibroblast migration velocity was significantly higher on soft polymeric substrata. Modulation of PIP2availability through neomycin treatment nearly doubled migration velocity on 10 kPa substrata, with significant increases on all stiffnesses. The distance between focal adhesions and the lamellar membrane (using wortmannin treatment to increase PIP2 via PI3K inhibition) was significantly shortest compared to untreated fibroblasts grown on the same surface. PIP2 localized to the leading edge of migrating fibroblasts more prominently in neomycin-treated cells. The membrane-bound protein, lamellipodin, did not vary under any condition. Additionally, fifteen micron-high micropost topography, which blocks migration, concentrates PIP2 near to the post. Actin dynamics within stress fibers, measured by fluorescence recovery after photobleaching, was not significantly different with stiffness, microtopography, nor with drug treatment. PIP2-modulating drugs delivered from microrod structures also affected migration velocity. Thus, manipulation of the microenvironment and lipid signaling regulatory drugs might be beneficial in improving therapeutics geared toward wound healing. |
| Databáze: | OpenAIRE |
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