Lipid signaling affects primary fibroblast collective migration and anchorage in response to stiffness and microtopography.
Lipid signaling affects primary fibroblast collective migration and anchorage in response to stiffness and microtopography.
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脂质信号传导会影响刚度和显微照片的一级成纤维细胞集体迁移和锚定。
DOI：
10.1002/jcp.26236
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发表时间：
2018-04
影响因子：
5.6
通讯作者：
Russell B
中科院分区：
文献类型：
--
作者：
Mkrtschjan MA;Gaikwad SB;Kappenman KJ;Solís C;Dommaraju S;Le LV;Desai TA;Russell B
细胞迁移受几种机械转导途径调节，其包括感知和转换机械微环境信号为内部生化细胞信号，如蛋白质磷酸化和脂质信号。虽然在理解机械转导背景下的蛋白质变化方面取得了重大进展，但脂质信号传导更难以研究。在这项研究中，物理线索的刚度（10千帕，100千帕，400千帕，和玻璃），微棒或微桩地形进行了操作，以重新编程原代成纤维细胞和评估的影响，脂质信号对肌动蛋白细胞骨架。在体外伤口闭合试验中，软聚合物基质上的原代心脏成纤维细胞迁移速度显著更高。通过新霉素处理的PIP 2可用性的调制几乎使10 kPa基质上的迁移速度加倍，所有刚度显著增加。与在相同表面上生长的未处理的成纤维细胞相比，粘着斑和层状膜（使用渥曼青霉素处理以通过PI3K抑制来增加PIP2）之间的距离显著最短。在新霉素处理的细胞中，PIP2更显著地定位于迁移成纤维细胞的前缘。膜结合蛋白，lamelipodin，在任何条件下都没有变化。此外，阻挡迁移的15微米高的微柱形貌将PIP2集中在柱附近。应力纤维内的肌动蛋白动力学，光漂白后的荧光恢复测量，与刚度，微地形，也没有显着不同的药物治疗。从微棒结构递送的PIP2调节药物也影响迁移速度。因此，操纵微环境和脂质信号调节药物可能有利于改善伤口愈合的治疗方法。
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.
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影响因子：
4.6
作者：
Chierico L;Joseph AS;Lewis AL;Battaglia G
通讯作者：
Battaglia G
DOI：
10.1016/j.bbrc.2012.11.120
发表时间：
2013-01-18
影响因子：
3.1
作者：
Doroudian, Golnar;Curtis, Matthew W.;Gang, Anjulie;Russell, Brenda
通讯作者：
Russell, Brenda
影响因子：
2
作者：
Harland B;Walcott S;Sun SX
通讯作者：
Sun SX
影响因子：
2.8
作者：
Poellmann, Michael J.;Johnson, Amy J. Wagoner
通讯作者：
Johnson, Amy J. Wagoner
影响因子：
4.6
作者：
Rouven Brückner B;Pietuch A;Nehls S;Rother J;Janshoff A
通讯作者：
Janshoff A