Condensed Matter Theory

Abstract:

Coordinated rotational motion is an intriguing, yet still elusive mode of collective cell migration, which is relevant in pathological and morphogenetic processes. Most of the studies on this topic have been carried out on epithelial cells plated on micropatterned substrates, where cell motion is confined in regions of well-defined shapes coated with extracellular matrix adhesive proteins. The driver of collective rotation in such conditions has not been clearly elucidated, although it has been speculated that spatial confinement can play an essential role in triggering cell rotation. Here, we study the growth of epithelial cell colonies freely expanding (i.e. with no physical constraints) on the surface of cell culture plates and focus on collective cell rotation in such conditions, a case which has received scarce attention in the literature. One of the main findings of our work is that coordinated cell rotation spontaneously occurs in cell clusters in the free growth regime, thus implying that cell confinement is not necessary to elicit collective rotation as previously suggested. The extent of collective rotation was size and shape dependent: a highly coordinated disc-like rotation was found in small cell clusters with a round shape, while collective rotation was suppressed in large irregular cell clusters generated by merging of different clusters in the course of their growth. The angular motion was persistent in the same direction, although clockwise and anticlockwise rotations were equally likely to occur among different cell clusters. Radial cell velocity was quite low as compared to the angular velocity, in agreement with the free expansion regime where cluster growth is essentially governed by cell proliferation. A clear difference in morphology was observed between cells at the periphery and the ones in the core of the clusters, the former being more elongated and spread out as compared to the latter. Overall, our results, to our knowledge, provide the first quantitative and systematic evidence that coordinated cell rotation does not require a spatial confinement and occurs spontaneously in freely expanding epithelial cell colonies, possibly as a mechanism for the system.

Abstract:

The design space for self-assembled multicomponent objects ranges from a solution in which every building block is unique to one with the minimum number of distinct building blocks that unambiguously define the target structure. We develop a pipeline to explore the design spaces for a set of structures of various sizes and complexities. To understand the implications of the different solutions, we analyze their assembly dynamics using patchy particle simulations and study the influence of the number of distinct building blocks, and the angular and spatial tolerances on their interactions, on the kinetics and yield of the target assembly. We show that the resource-saving solution with a minimum number of distinct blocks can often assemble just as well (or faster) than designs where each building block is unique. We further use our methods to design multifarious structures, where building blocks are shared between different target structures. Finally, we use coarse-grained DNA simulations to investigate the realization of multicomponent shapes using DNA nanostructures as building blocks.