The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro
The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro
复制标题
DOI：
10.1016/j.yexcr.2004.03.035
复制
发表时间：
2004-07-15
影响因子：
3.7
通讯作者：
Gooch, KJ
中科院分区：
文献类型：
--
作者：
Sieminski, AL;Hebbel, RP;Gooch, KJ
当悬浮在胶原凝胶中时，内皮细胞伸长并形成含有管腔的毛细血管样网络。人血液生长内皮细胞（HBOEC）悬浮在相对刚性的3 mg/ml漂浮胶原凝胶中，形成体内样的、薄的、分支的多细胞结构，具有小的厚壁管腔，而人脐静脉内皮细胞（HUVEC）形成较少的多细胞结构，具有铺展的外观，并且具有较大的管腔。HBOEC比HUVEC对胶原蛋白凝胶施加更多的牵引力，如漂浮凝胶的更大收缩所证明的。当通过将胶原蛋白浓度从3 mg/ml降低至1.5 mg/ml来降低漂浮凝胶的刚度时，HUVEC更多地收缩凝胶并形成具有小管腔的薄的多细胞结构，其外观与漂浮3 mg/ml凝胶中的HBOEC相似。与漂浮凝胶相反，在机械约束的凝胶中由细胞施加的牵引力遇到相当大的阻力。在约束胶原蛋白凝胶（3毫克/毫升），这两种细胞类型出现蔓延，形成的结构与较少的细胞，有较大的，薄壁管腔比浮动凝胶，并显示出突出的肌动蛋白应力纤维，没有看到浮动凝胶。这些结果表明，细胞力的产生和表观基质刚度的相对幅度调节毛细血管形态发生在体外，这种平衡可能在调节体内血管生成中发挥作用。(C)2004年爱思唯尔公司All rights reserved.
When suspended in collagen gels, endothelial cells elongate and form capillary-like networks containing lumens. Human blood outgrowth endothelial cells (HBOEC) suspended in relatively rigid 3 mg/ml floating collagen gels, formed in vivo-like, thin, branched multi-cellular structures with small, thick-walled lumens, while human umbilical vein endothelial cells (HUVEC) formed fewer multi-cellular structures, had a spread appearance, and had larger lumens. HBOEC exert more traction on collagen gels than HUVEC as evidenced by greater contraction of floating gels. When the stiffness of floating gels was decreased by decreasing the collagen concentration from 3 to 1.5 mg/ml, HUVEC contracted gels more and formed thin, multi-cellular structures with small lumens, similar in appearance to HBOEC in floating 3 mg/ml gels. In contrast to floating gels, traction forces exerted by cells in mechanically constrained gels encounter considerable resistance. In constrained collagen gels (3 mg/ml), both cell types appeared spread, formed structures with fewer cells, had larger, thinner-walled lumens than in floating gels, and showed prominent actin stress fibers, not seen in floating gels. These results suggest that the relative magnitudes of cellular force generation and apparent matrix stiffness modulate capillary morphogenesis in vitro and that this balance may play a role in regulating angiogenesis in vivo. (C) 2004 Elsevier Inc. All rights reserved.