skip to main content


Title: Substrate-rigidity dependent migration of an idealized twitching bacterium
Mechanical properties of the extracellular matrix are important determinants of cellular migration in diverse processes, such as immune response, wound healing, and cancer metastasis. Moreover, recent studies indicate that even bacterial surface colonization can depend on the mechanics of the substrate. Here, we focus on physical mechanisms that can give rise to substrate-rigidity dependent migration. We study a “twitcher”, a cell driven by extension–retraction cycles, to idealize bacteria and perhaps eukaryotic cells that employ a slip-stick mode of motion. The twitcher is asymmetric and always pulls itself forward at its front. Analytical calculations show that the migration speed of a twitcher depends non-linearly on substrate rigidity. For soft substrates, deformations do not lead to build-up of significant force and the migration speed is therefore determined by stochastic adhesion unbinding. For rigid substrates, forced adhesion rupture determines the migration speed. Depending on the force-sensitivity of front and rear adhesions, forced bond rupture implies an increase or a decrease of the migration speed. A requirement for the occurrence of rigidity-dependent stick-slip migration is a “sticky” substrate, with binding rates being an order of magnitude larger than unbinding rates in absence of force. Computer simulations show that small stall forces of the driving machinery lead to a reduced movement on high rigidities, regardless of force-sensitivities of bonds. The simulations also confirm the occurrence of rigidity-dependent migration speed in a generic model for slip-stick migration of cells on a sticky substrate.  more » « less
Award ID(s):
1734030
NSF-PAR ID:
10169888
Author(s) / Creator(s):
; ; ; ; ; ;
Date Published:
Journal Name:
Soft Matter
Volume:
15
Issue:
30
ISSN:
1744-683X
Page Range / eLocation ID:
6224 to 6236
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Adhesive cell–substrate interactions are crucial for cell motility and are responsible for the necessary traction that propels cells. These interactions can also change the shape of the cell, analogous to liquid droplet wetting on adhesive substrates. To address how these shape changes affect cell migration and cell speed we model motility using deformable, 2D cross-sections of cells in which adhesion and frictional forces between cell and substrate can be varied separately. Our simulations show that increasing the adhesion results in increased spreading of cells and larger cell speeds. We propose an analytical model which shows that the cell speed is inversely proportional to an effective height of the cell and that increasing this height results in increased internal shear stress. The numerical and analytical results are confirmed in experiments on motile eukaryotic cells. 
    more » « less
  2. Protein adsorption to solid carbohydrate interfaces is critical to many biological processes, particularly in biomass deconstruction. To engineer more-efficient enzymes for biomass deconstruction into sugars, it is necessary to characterize the complex protein–carbohydrate interfacial interactions. A carbohydrate-binding module (CBM) is often associated with microbial surface-tethered cellulosomes or secreted cellulase enzymes to enhance substrate accessibility. However, it is not well known how CBMs recognize, bind, and dissociate from polysaccharides to facilitate efficient cellulolytic activity, due to the lack of mechanistic understanding and a suitable toolkit to study CBM–substrate interactions. Our work outlines a general approach to study the unbinding behavior of CBMs from polysaccharide surfaces using a highly multiplexed single-molecule force spectroscopy assay. Here, we apply acoustic force spectroscopy (AFS) to probe a Clostridium thermocellum cellulosomal scaffoldin protein (CBM3a) and measure its dissociation from nanocellulose surfaces at physiologically relevant, low force loading rates. An automated microfluidic setup and method for uniform deposition of insoluble polysaccharides on the AFS chip surfaces are demonstrated. The rupture forces of wild-type CBM3a, and its Y67A mutant, unbinding from nanocellulose surfaces suggests distinct multimodal CBM binding conformations, with structural mechanisms further explored using molecular dynamics simulations. Applying classical dynamic force spectroscopy theory, the single-molecule unbinding rate at zero force is extrapolated and found to agree with bulk equilibrium unbinding rates estimated independently using quartz crystal microbalance with dissipation monitoring. However, our results also highlight critical limitations of applying classical theory to explain the highly multivalent binding interactions for cellulose–CBM bond rupture forces exceeding 15 pN. 
    more » « less
  3. Abstract

    Strain gradients widely exist in development and physiological activities. The directional movement of cells is essential for proper cell localization, and directional cell migration in responses to gradients of chemicals, rigidity, density, and topography of extracellular matrices have been well‐established. However; it is unclear whether strain gradients imposed on cells are sufficient to drive directional cell migration. In this work, a programmable uniaxial cell stretch device is developed that creates controllable strain gradients without changing substrate stiffness or ligand distributions. It is demonstrated that over 60% of the single rat embryonic fibroblasts migrate toward the lower strain side in static and the 0.1 Hz cyclic stretch conditions at ≈4% per mm strain gradients. It is confirmed that such responses are distinct from durotaxis or haptotaxis. Focal adhesion analysis confirms higher rates of contact area and protrusion formation on the lower strain side of the cell. A 2D extended motor‐clutch model is developed to demonstrate that the strain‐introduced traction force determines integrin fibronectin pairs' catch‐release dynamics, which drives such directional migration. Together, these results establish strain gradient as a novel cue to regulate directional cell migration and may provide new insights in development and tissue repairs.

     
    more » « less
  4. Abstract

    Utilizing colloidal probe, lateral force microscopy and simultaneous confocal microscopy, combined with finite element analysis, we investigate how a microparticle starts moving laterally on a soft, adhesive surface. We find that the surface can form a self-contacting crease at the leading front, which results from a buildup of compressive stress. Experimentally, creases are observed on substrates that exhibit either high or low adhesion when measured in the normal direction, motivating the use of simulations to consider the role of adhesion energy and interfacial strength. Our simulations illustrate that the interfacial strength plays a dominating role in the nucleation of a crease. After the crease forms, it progresses through the contact zone in a Schallamach wave-like fashion. Interestingly, our results suggest that this Schallamach wave-like motion is facilitated by free slip at the adhesive, self-contacting interface within the crease.

     
    more » « less
  5. Atherosclerosis-related cardiovascular diseases are a leading cause of mortality worldwide. Vascular smooth muscle cells (VSMCs) comprise the medial layer of the arterial wall and undergo phenotypic switching during atherosclerosis to a synthetic phenotype capable of proliferation and migration. The surrounding environment undergoes alterations in extracellular matrix (ECM) stiffness and composition in addition to an increase in addition to an increase in cholesterol content. Using an atherosclerotic murine model, we analyzed how the mechanics of VSMCs isolated from western diet fed apolipoprotein-E knockout (ApoE -/- ) and wild type (WT) mice were altered during atherosclerosis. Increased stiffness of ApoE -/- VSMCs correlated with a greater degree of stress fiber alignment as evidenced by atomic force microscopy (AFM)-generated force maps and stress fiber topography images. On type-1 collagen (COL1)-coated polyacrylamide (PA) gels of varying stiffness, WT VSMCs had higher adhesion forces to N-Cadherin (N-Cad) and COL1. ApoE -/- VSMC stiffness was significantly greater than WT cells with increased cell stiffness with increasing substrate stiffness for both ApoE -/- and WT VSMCs . In addition, ApoE -/- VSMCs showed an enhanced migration capability on COL1-coated substrates and a general decreasing trend in migration capacity with increasing substrate stiffness, correlating with the lower adhesion forces as compared to WT VSMCs. Altogether, these results demonstrate the potential contribution of the alteration in VSMC mechanics in the development of atherosclerosis. 
    more » « less