Deterministic model of dermal wound invasion incorporating receptor-mediated signal transduction and spatial gradient sensing
Deterministic model of dermal wound invasion incorporating receptor-mediated signal transduction and spatial gradient sensing
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DOI：
10.1529/biophysj.105.077610
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发表时间：
2006-04-01
影响因子：
3.4
通讯作者：
Haugh, JM
中科院分区：
文献类型：
--
作者：
Haugh, JM
在皮肤伤口愈合过程中，血小板衍生生长因子（PDGF）作为成纤维细胞的化学引诱物和有丝分裂原，在数天内有效刺激它们侵入纤维蛋白凝块。这个过程的数学模型，它准确地占PDGF梯度传感通过PDGF受体/磷酸肌醇3-激酶介导的信号转导的灵敏度。模型的分析表明，PDGF受体介导的内吞作用和PDGF的降解允许恒定的PDGF浓度pro。LE保持在成纤维细胞密度亲的前端。当它以恒定的速率传播到凝块中时。因此，恒定的PDGF梯度可以跨越不对称磷酸肌醇3-激酶信号传导和成纤维细胞趋化性的最佳浓度范围，在相对宽的PDGF分泌速率范围内引起接近最大的侵袭速率。一个有点令人惊讶的发现是，非常尖锐的PDGF梯度不一定刺激通过凝块的更快进展，因为通过PDGF消耗维持这样的梯度是一个潜在的限速过程。
During dermal wound healing, platelet-derived growth factor (PDGF) serves as both a chemoattractant and mitogen for fibroblasts, potently stimulating their invasion of the fibrin clot over a period of several days. A mathematical model of this process is presented, which accurately accounts for the sensitivity of PDGF gradient sensing through PDGF receptor/phosphoinositide 3-kinase-mediated signal transduction. Analysis of the model suggests that PDGF receptor-mediated endocytosis and degradation of PDGF allows a constant PDGF concentration pro. le to be maintained at the leading front of the fibroblast density pro. le as it propagates, at a constant rate, into the clot. Thus, the constant PDGF gradient can span the optimal concentration range for asymmetric phosphoinositide 3-kinase signaling and fibroblast chemotaxis, with near-maximal invasion rates elicited over a relatively broad range of PDGF secretion rates. A somewhat surprising finding was that extremely sharp PDGF gradients do not necessarily stimulate faster progression through the clot, because maintaining such a gradient through PDGF consumption is a potentially rate-limiting process.