George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA, 30332-0405, USA.
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, 30322, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA, 30332, USA; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, 30332, USA; Institute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Biomaterials. 2021 Jul;274:120828. doi: 10.1016/j.biomaterials.2021.120828. Epub 2021 Apr 23.
Physiological processes such as blood clotting and wound healing as well as pathologies such as fibroses and musculoskeletal contractures, all involve biological materials composed of a contracting cellular population within a fibrous matrix, yet how the microscale interactions among the cells and the matrix lead to the resultant emergent behavior at the macroscale tissue level remains poorly understood. Platelets, the anucleate cell fragments that do not divide nor synthesize extracellular matrix, represent an ideal model to study such systems. During blood clot contraction, microscopic platelets actively pull fibers to shrink the macroscale clot to less than 10% of its initial volume. We discovered that platelets utilize a new emergent behavior, asynchrono-mechanical amplification, to enhanced volumetric material contraction and to magnify contractile forces. This behavior is triggered by the heterogeneity in the timing of a population of actuators. This result indicates that cell heterogeneity, often attributed to stochastic cell-to-cell variability, can carry an essential biophysical function, thereby highlighting the importance of considering 4 dimensions (space + time) in cell-matrix biomaterials. This concept of amplification via heterogeneity can be harnessed to increase mechanical efficiency in diverse systems including implantable biomaterials, swarm robotics, and active polymer composites.
生理过程如血液凝固和伤口愈合以及纤维化和肌肉骨骼挛缩等病理学过程,都涉及由纤维基质内收缩细胞群体组成的生物材料,但细胞和基质之间的微观相互作用如何导致宏观组织水平的结果性 emergent 行为仍知之甚少。血小板是无核细胞碎片,既不分裂也不合成细胞外基质,是研究此类系统的理想模型。在血液凝结收缩过程中,微观血小板积极拉动纤维,将宏观凝结物收缩到初始体积的 10%以下。我们发现,血小板利用一种新的 emergent 行为,异步机械放大,增强体积材料收缩并放大收缩力。这种行为是由一群执行器的时间异质性触发的。这一结果表明,细胞异质性通常归因于随机的细胞间变异性,可以发挥重要的生物物理功能,从而强调了在细胞基质生物材料中考虑 4 个维度(空间+时间)的重要性。通过异质性放大的概念可以用于提高包括可植入生物材料、群体机器人技术和活性聚合物复合材料在内的各种系统的机械效率。