Adhesion strength and contractility enable metastatic cells to become adurotactic

Yeoman, Benjamin; Shatkin, Gabriel; Beri, Pranjali; Banisadr, Afsheen; Katira, Parag; Engler, Adam J.

doi:10.1016/j.celrep.2021.108816

Cited by 42 publications

(39 citation statements)

References 70 publications

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“…There is an optimal adhesion size that maximizes traction force, past which, the traction force decreases. These results could explain how highly motile cells exhibit inverse correlation between adhesion size, migration speed, and increased invasiveness [3,67,77]. Increasing forces increases the likelihood that integrins will rupture their bond with the substrate and decreases the bond lifetime.…”

Section: Discussionmentioning

confidence: 98%

Chemo-Mechanical Factors That Limit Cellular Force Generation

et al. 2022

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Cellular traction forces that are dependent on actin-myosin activity are necessary for numerous developmental and physiological processes. As traction force emerges as a promising cancer biomarker there is a growing need to understand force generation in response to chemical and mechanical cues. Our goal is to present a unified modeling framework that integrates actin-myosin activity, substrate stiffness, integrin bond type, and adhesion complex dynamics to explain how force develops under specific conditions. Our simulation results show that substrate stiffness and number of myosin motors contribute to the maximum actin-myosin forces that can be generated but do not solely control the force transmitted by the cells to the surface, i.e., the traction force. The kinetics of the bonds between the cell and the substrate plays an equally important role. Overall, we find that while the cell can generate large actin-myosin forces in individual stress fibers (> 300 pN), the maximum force transmitted to the surface per cell-substrate attachment only reaches a fraction of these values (approx. 50 pN). Traction stress, the sum of forces transferred by all cell-substrate attachments in a unit area, is biphasic or sigmoidal with increasing substrate stiffness depending on the number of active myosin motors generating forces. Finally, we conclude that adhesions < 1 μm2 generate widely variable traction forces and that impulse, the magnitude and duration of a force generating event, is a key limiting factor in traction stress.

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Section: Discussionmentioning

confidence: 98%

Chemo-Mechanical Factors That Limit Cellular Force Generation

et al. 2022

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“…Of note, according to the molecular clutch hypothesis, such forces may not be optimally transmitted depending on substrate features (e.g., stiffness, viscoelasticity, and stored strain energy) [ 103 , 187 , 194 ]. An enhanced actomyosin activity and cell contractility enable cells to migrate against stiffness gradients [ 195 ]. Therefore, metastatic cells (e.g., mammary, lung, prostate) may exhibit an adurotactic behavior in their tumor-specific niche.…”

Section: Mechanics Of Cell Migrationmentioning

confidence: 99%

Unravelling cell migration: defining movement from the cell surface

Merino-Casallo

Gómez‐Benito

Hervas-Raluy

et al. 2022

Cell Adhesion & Migration

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Cell motility is essential for life and development. Unfortunately, cell migration is also linked to several pathological processes, such as cancer metastasis. Cells’ ability to migrate relies on many actors. Cells change their migratory strategy based on their phenotype and the properties of the surrounding microenvironment. Cell migration is, therefore, an extremely complex phenomenon. Researchers have investigated cell motility for more than a century. Recent discoveries have uncovered some of the mysteries associated with the mechanisms involved in cell migration, such as intracellular signaling and cell mechanics. These findings involve different players, including transmembrane receptors, adhesive complexes, cytoskeletal components , the nucleus, and the extracellular matrix. This review aims to give a global overview of our current understanding of cell migration.

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“…We tested three different force-lifetime relations for the adhesions, varying for maximum lifetime, 𝜏 𝑚𝑎𝑥 (Figure 4A). The breaking point for the actin-adhesion bond, or force corresponding to 𝜏 𝑚𝑎𝑥 , was set at 30 pN [48][49][50]. The peaks in lifetime were either 3 s, 7.5 s, or 12 s, typical behavior of integrin unbinding from fibronectin under load [48].…”

Section: The Lifetime Of Nascent Adhesions Regulates the Velocity Of The Membranementioning

confidence: 99%

Nascent adhesions differentially regulate lamellipodium velocity and persistence

Carney

Khan

Samson

et al. 2021

Preprint

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Cell migration is essential to physiological and pathological biology. Migration is driven by the motion of a leading edge, in which actin polymerization pushes against the edge and adhesions transmit traction to the substrate while membrane tension increases. How the actin and adhesions synergistically control edge protrusion remains elusive. We addressed this question by developing a computational model in which the Brownian ratchet mechanism governs actin filament polymerization against the membrane and the molecular clutch mechanism governs adhesion to the substrate (BR-MC model). Our model predicted that actin polymerization is the most significant driver of protrusion, as actin had a greater effect on protrusion than adhesion assembly. Increasing the lifetime of nascent adhesions also enhanced velocity, but decreased the protrusion’s motional persistence, because filaments maintained against the cell edge ceased polymerizing as membrane tension increased. We confirmed the model predictions with measurement of adhesion lifetime and edge motion in migrating cells. Adhesions with longer lifetime were associated with faster protrusion velocity and shorter persistence. Experimentally increasing adhesion lifetime increased velocity but decreased persistence. We propose a mechanism for actin polymerization-driven, adhesion-dependent protrusion in which balanced nascent adhesion assembly and lifetime generates protrusions with the power and persistence to drive migration.

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Adhesion strength and contractility enable metastatic cells to become adurotactic

Cited by 42 publications

References 70 publications

Chemo-Mechanical Factors That Limit Cellular Force Generation

Chemo-Mechanical Factors That Limit Cellular Force Generation

Unravelling cell migration: defining movement from the cell surface

Nascent adhesions differentially regulate lamellipodium velocity and persistence

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