Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna väg 9, Solna 171 65, Sweden.
J R Soc Interface. 2019 Oct 31;16(159):20190299. doi: 10.1098/rsif.2019.0299. Epub 2019 Oct 30.
Adhesive interactions between cells play an integral role in development, differentiation and regeneration. Existing methods for controlling cell-cell cohesion and adhesion by manipulating protein expression are constrained by biological interdependencies, e.g. coupling of cadherins to actomyosin force-feedback mechanisms. We use oligonucleotides conjugated to PEGylated lipid anchors (ssDNAPEGDPPE) to introduce artificial cell-cell adhesion that is largely decoupled from the internal cytoskeleton. We describe cell-cell doublets with a mechanical model based on isotropic, elastic deformation of spheres to estimate the adhesion at the cell-cell interface. Physical manipulation of adhesion by modulating the PEG-lipid to ssDNAPEGDPPE ratio, and conversely treating with actin-depolymerizing cytochalasin D, resulted in decreases and increases in doublet contact area, respectively. Our data are relevant to the ongoing discussion over mechanisms of tissue surface tension and in agreement with models based on opposing cortical and cohesive forces. PEG-lipid modulation of doublet geometries resulted in a well-defined curve indicating continuity, enabling prescriptive calibration for controlling doublet geometry. Our study demonstrates tuning of basic doublet adhesion, laying the foundation for more complex multicellular adhesion control independent of protein expression.
细胞间的黏附相互作用在发育、分化和再生中起着至关重要的作用。通过操纵蛋白质表达来控制细胞间黏附和黏附的现有方法受到生物相关性的限制，例如钙黏蛋白与肌动球蛋白力反馈机制的偶联。我们使用与聚乙二醇化脂质锚定物（ssDNAPEGDPPE）缀合的寡核苷酸来引入人工细胞间黏附，这种黏附在很大程度上与细胞内细胞骨架分离。我们基于各向同性、弹性球体变形的机械模型来描述细胞-细胞二联体，以估计细胞-细胞界面处的黏附力。通过调节聚乙二醇化脂质与 ssDNAPEGDPPE 的比例来物理操纵黏附，并用肌动蛋白解聚细胞松弛素 D 进行相反处理，分别导致二联体接触面积减少和增加。我们的数据与组织表面张力机制的持续讨论相关，并与基于相反的皮质和内聚的力的模型一致。二联体几何形状的聚乙二醇化脂质调节导致了一条明确的曲线，表明连续性，从而能够对控制二联体几何形状进行规定性校准。我们的研究表明基本二联体黏附的调节，为独立于蛋白质表达的更复杂的多细胞黏附控制奠定了基础。
