Mechanical Causation of Biological Structure: Productive Pulls Produce Persistent Filaments in a Human Fibroblast Model of Matrix Development

Abstract

During development, mesenchymal cells direct the elaboration of extracellular matrix that shapes the initial animal bauplan which subsequently grows to produce mechanically-competent structure. To gain insight into the processes that initiate matrix formation at the cellular level, high temporal and spatial resolution videos were obtained from a primary human corneal fibroblast (PHCF) cell culture system known to produce an organized, collagenous stroma similar to a human cornea. The images were taken over a 4-day period prior to culture confluency which permitted a clear view of the cell kinematics and any elaborated filaments. The movies reveal an active cellular system in which the PHCFs execute five types of high-velocity and high extensional strain-rate 'pulls' that produce persistent filaments. In four of the pull types, average maximum strain rates (~0.1-0.33s-1) were adequate to induce aggregation and/or crystallization in crowded biopolymer systems. The results demonstrate that PHCFs have the capacity to mechanically induce the formation of biopolymer structures intercellularly and in the path of force.