Simpson D G, Terracio L, Terracio M, Price R L, Turner D C, Borg T K
Department of Developmental Biology and Anatomy, University of South Carolina Medical School, Columbia 29208.
J Cell Physiol. 1994 Oct;161(1):89-105. doi: 10.1002/jcp.1041610112.
Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac alpha 1 beta 1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. Individual NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependent upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac alpha 1 beta 1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac alpha 1 or beta 1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac alpha 1 beta 1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.
细胞表型是细胞内在遗传程序与形态发生信号之间动态相互作用的结果，形态发生信号用于调节该程序的表达程度。在本研究中，我们研究了形态发生信息如何存储在细胞外基质（ECM）中，并通过心脏α1β1整合素分子传递给新生心脏细胞（NHC）。制备了具有确定取向的I型胶原薄膜（T1C）。这是通过将T1C应用于100 mm培养皿的周边来实现的。然后用无菌细胞刮刀以连续的笔触将T1C拉过培养皿表面并使其聚合。当NHC在该基质上培养时，它们作为一个群体沿着与凝胶晶格平行的共同轴扩散，并表现出类似体内的表型。单个NHC呈现出细长的棒状形状，并显示出平行排列的肌原纤维。这些表型特征在原代培养中至少维持4周。这种组织样组织模式的演变取决于NHC与由心脏α1β1整合素复合物介导的基于胶原的基质之间的特定相互作用。这一结论得到了各种实验结果的支持。改变基质的三级结构或阻断心脏α1或β1整合素链的细胞外结构域会抑制组织样组织模式的表达。细胞间接触或收缩功能都不是诱导棒状细胞形状形成所必需的。然而，搏动活动对于组装分化良好的肌原纤维装置是必需的。这些数据表明，心脏α1β1整合素复合物用于检测和转导存储在周围基质三级结构中的表型信息。
