Toward the reconstitution of synthetic cell motility

Abstract

Cellular motility is a fundamental process essential for embryonic development, wound healing, immune responses, and tissues development. Cells are mostly moving by crawling on external, or inside, substrates which can differ in their surface composition, geometry, and dimensionality. Cells can adopt different migration phenotypes, e.g., bleb-based and protrusion-based, depending on myosin contractility, surface adhesion, and cell confinement. In the few past decades, research on cell motility has focused on uncovering the major molecular players and their order of events. Despite major progresses, our ability to infer on the collective behavior from the molecular properties remains a major challenge, especially because cell migration integrates numerous chemical and mechanical processes that are coupled via feedbacks that span over large range of time and length scales. For this reason, reconstituted model systems were developed. These systems allow for full control of the molecular constituents and various system parameters, thereby providing insight into their individual roles and functions. In this review we describe the various reconstituted model systems that were developed in the past decades. Because of the multiple steps involved in cell motility and the complexity of the overall process, most of the model systems focus on very specific aspects of the individual steps of cell motility. Here we describe the main advancement in cell motility reconstitution and discuss the main challenges toward the realization of a synthetic motile cell.

Toward Artificial Cells: Novel Advances in Energy Conversion and Cellular Motility

“…Thus, the creation of artificial cell‐like structures by using bottom‐up biology is an expanding research field that aims to understand the mechanisms underlying biological processes via in vitro assembly of their essential components into artificial cells. In this regard, the method and the research imparting motility as living cells for cell‐like objects have been actively studied with reconstitution of bleb‐based migration with nonspecific (low) adhesion and protrusion‐based migration with specific (strong) adhesion, and more recently, protrusion‐based migration with specific adhesion, as well as photoswitchable protein interactions on the surface of an artificial cell, induced by light …”

Mimicking Adhesion in Minimal Synthetic Cells

“…[18] For example during cell motility, the cell dynamically has to alter its adhesions to move in a defined direction; the cell forms more and new adhesions to the matrix at the leading edge as it dissembles existing adhesions at the trailing edge. Among these, the adhesion of cells through integrin transmembrane receptors to extracellular matrix proteins such as fibronectin, collagen, and fibrinogen are the best most studied.…”

“…Another layer of complexity in cell-matrix adhesions comes from their dynamics and their spatiotemporal regulation during different cell events including wound healing, immune response, and embryonic and tissue development. [18] For example during cell motility, the cell dynamically has to alter its adhesions to move in a defined direction; the cell forms more and new adhesions to the matrix at the leading edge as it dissembles existing adhesions at the trailing edge. Given the complexity of cellmatrix adhesion from the molecular, biophysical, signaling, and spatiotemporal control perspective, it is obvious that it is a challenge to reconstitute cell-adhesions from the bottom-up.…”

“…[27] A prime example of spatiotemporal control over cell-matrix adhesions is observed during cell motility. [18] As the cell moves forward, it assembles new adhesions at the leading edge at the same rate as it disassembles them at the trailing edge. [7] This requires regulating the adhesions in space at subcellular spatial Adv.…”

Engineering Light‐Responsive Contractile Actomyosin Networks with DNA Nanotechnology

“…[1,2] Conventionally, biomolecules, often proteins, have been isolated from cells and reconstituted in cell-sized confinement to reconstruct versatile cellular functions and sophisticated processes like adhesion, [3][4][5] energy generation, [6,7] or motility. [8][9][10] For efficient encapsulation of biocontent, droplet-based microfluidics proved to be a very useful technique due to its high degree of controllability and high-throughput formation of monodisperse compartments. [3,[11][12][13][14] In particular, actin networks have been reconstituted into water-in-oil droplets [15][16][17] and giant unilamellar vesicles [18][19][20] to observe the role of specific proteins regulating cellular morphology.…”