Adhesion strength between cells regulate nonmonotonic growth by a biomechanical feedback mechanism
Adhesion strength between cells regulate nonmonotonic growth by a biomechanical feedback mechanism
复制标题
细胞之间的粘附强度通过生物力学反馈机制调节非单调生长
DOI：
10.1016/j.bpj.2022.04.032
复制
发表时间：
2022
影响因子：
3.4
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
--
作者：
Malmi-Kakkada, Abdul N.;Sinha, Sumit;Li, Xin;Thirumalai, D.
我们确定了细胞间的相互作用和机械压力所经历的单细胞调节细胞增殖使用一个最小的计算模型的三维多细胞球体（MCS）的增长。我们发现，细胞分裂率的空间变化取决于细胞在MCS内的核心或外围位置，受细胞间粘附强度的调节（）。变化导致MCS中细胞的非单调增殖。一个生物力学反馈机制耦合的和微环境依赖的压力波动相对于阈值（）决定了休眠期的开始，并解释了非单调的增殖反应。从低值增加增强细胞增殖，因为单个细胞上的压力比。然而，在高温下，细胞很容易休眠，不能在时空中有效地重新排列，导致细胞增殖停滞。利用我们的理论预测，我们解释实验数据的粘附强度对细胞增殖的影响，并找到很好的协议。我们的工作表明，细胞增殖受压力-粘附反馈机制的调控，这可能是多细胞生长的一个普遍特征。
We determine how intercellular interactions and mechanical pressure experienced by single cells regulate cell proliferation using a minimal computational model for three-dimensional multicellular spheroid (MCS) growth. We discover that emergent spatial variations in the cell division rate, depending on the location of the cells either at the core or periphery within the MCS, is regulated by intercellular adhesion strength (). Varyingresults in nonmonotonic proliferation of cells in the MCS. A biomechanical feedback mechanism coupling theand microenvironment-dependent pressure fluctuations relative to a threshold value () determines the onset of a dormant phase, and explains the nonmonotonic proliferation response. Increasingfrom low values enhances cell proliferation because pressure on individual cells is smaller compared with. However, at high, cells readily become dormant and cannot rearrange effectively in spacetime, leading to arrested cell proliferation. Utilizing our theoretical predictions, we explain experimental data on the impact of adhesion strength on cell proliferation and find good agreement. Our work, which shows that proliferation is regulated by pressure-adhesion feedback mechanism, may be a general feature of multicellular growth.