Bimodal sensing of guidance cues in mechanically distinct microenvironments

Erdem D. Tabdanov, Paolo Provenzano

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Contact guidance due to extracellular matrix architecture is a key regulator of carcinoma invasion and metastasis, yet our understanding of how cells sense guidance cues is limited. Here, using a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions, we demonstrate distinct mechanoresponsive behavior. Through disruption of traction forces, we observe a profound phenotypic shift towards a mode of dendritic protrusion and identify bimodal processes that govern guidance sensing. In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.
Original languageEnglish (US)
JournalNature Communications
StatePublished - Nov 20 2018

Fingerprint

cues
Fluidics
Cadherins
Cues
Adhesion
Cells
Stiffness
Traction
Mechanical properties
Carcinoma
disrupting
traction
Microtubules
Extracellular Matrix
cancer
Neoplasm Metastasis
fluidics
regulators
metastasis
matrices

Cite this

Bimodal sensing of guidance cues in mechanically distinct microenvironments. / Tabdanov, Erdem D.; Provenzano, Paolo.

In: Nature Communications, 20.11.2018.

Research output: Contribution to journalArticle

@article{419ca271c3f448b6a88f9664fb60dbab,
title = "Bimodal sensing of guidance cues in mechanically distinct microenvironments",
abstract = "Contact guidance due to extracellular matrix architecture is a key regulator of carcinoma invasion and metastasis, yet our understanding of how cells sense guidance cues is limited. Here, using a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions, we demonstrate distinct mechanoresponsive behavior. Through disruption of traction forces, we observe a profound phenotypic shift towards a mode of dendritic protrusion and identify bimodal processes that govern guidance sensing. In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.",
author = "Tabdanov, {Erdem D.} and Paolo Provenzano",
year = "2018",
month = "11",
day = "20",
language = "English (US)",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Bimodal sensing of guidance cues in mechanically distinct microenvironments

AU - Tabdanov, Erdem D.

AU - Provenzano, Paolo

PY - 2018/11/20

Y1 - 2018/11/20

N2 - Contact guidance due to extracellular matrix architecture is a key regulator of carcinoma invasion and metastasis, yet our understanding of how cells sense guidance cues is limited. Here, using a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions, we demonstrate distinct mechanoresponsive behavior. Through disruption of traction forces, we observe a profound phenotypic shift towards a mode of dendritic protrusion and identify bimodal processes that govern guidance sensing. In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.

AB - Contact guidance due to extracellular matrix architecture is a key regulator of carcinoma invasion and metastasis, yet our understanding of how cells sense guidance cues is limited. Here, using a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions, we demonstrate distinct mechanoresponsive behavior. Through disruption of traction forces, we observe a profound phenotypic shift towards a mode of dendritic protrusion and identify bimodal processes that govern guidance sensing. In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.

M3 - Article

C2 - 30459308

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -