Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, USA.
J Mech Behav Biomed Mater. 2013 Dec;28:125-46. doi: 10.1016/j.jmbbm.2013.07.018. Epub 2013 Aug 2.
Wounds in the embryo show a remarkable ability to heal quickly without leaving a scar. Previous studies have found that an actomyosin ring (purse string) forms around the wound perimeter and contracts to close the wound over the course of several dozens of minutes. Here, we report experiments that reveal an even faster mechanism which remarkably closes wounds by more than 50% within the first 30s. Circular and elliptical wounds (~100μm in size) were made in the blastoderm of early chick embryos and allowed to heal, with wound area and shape characterized as functions of time. The closure rate displayed a biphasic behavior, with rapid constriction lasting about a minute, followed by a period of more gradual closure to complete healing. Fluorescent staining suggests that both healing phases are driven by actomyosin contraction, with relatively rapid contraction of fibers at cell borders within a relatively thick ring of tissue (several cells wide) around the wound followed by slower contraction of a thin supracellular actomyosin ring along the margin, consistent with a purse string mechanism. Finite-element modeling showed that this idea is biophysically plausible, with relatively isotropic contraction within the thick ring giving way to tangential contraction in the thin ring. In addition, consistent with experimental results, simulated elliptical wounds heal with little change in aspect ratio, and decreased membrane tension can cause these wounds to open briefly before going on to heal. These results provide new insight into the healing mechanism in embryonic epithelia.
胚胎中的伤口显示出一种惊人的快速愈合能力,而不会留下疤痕。先前的研究发现,伤口周边会形成一个肌动球蛋白环(束带),并在几十分钟的过程中收缩以闭合伤口。在这里,我们报告了一些实验,这些实验揭示了一种更快的机制,即在最初的 30 秒内,伤口就能惊人地闭合超过 50%。在早期鸡胚的胚盘上制造圆形和椭圆形的伤口(大小约为 100μm),并让其自行愈合,通过时间的函数来描述伤口面积和形状的变化。伤口的闭合速度呈现出双相行为,快速收缩持续约一分钟,随后是一段更缓慢的闭合过程,直到完全愈合。荧光染色表明,两个愈合阶段都是由肌动球蛋白收缩驱动的,在伤口周围相对较厚的组织环(几细胞宽)内的细胞边界处,纤维相对快速地收缩,随后是沿着边缘的较薄的超细胞肌动球蛋白环的较慢收缩,这与束带机制一致。有限元建模表明,这个想法在生物学上是合理的,较厚环内的各向同性收缩逐渐转变为较薄环内的切线收缩。此外,与实验结果一致,模拟的椭圆形伤口在愈合过程中纵横比几乎没有变化,而膜张力的降低会导致这些伤口短暂张开,然后继续愈合。这些结果为胚胎上皮的愈合机制提供了新的见解。