Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread

Deok Ho Kim, Andrew Ewald, Jin Seok Park, Kshitiz, Moonkyu Kwak, Ryan S. Gray, Chia Yi Su, Jayhyun Seo, Steven An, Andre Levchenko

Research output: Contribution to journalArticle

Abstract

The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix. When this re-organization is mimicked using a nano-fabricated model of aligned extracellular matrix fibers, metastatic cells, including less invasive melanoma cells, were in turn induced to align, elongate and migrate, guided by the local ridge orientations. Strikingly, we found that this aligned migration of melanoma cells was accompanied by long-range regulation of cytoskeletal remodeling that show anisotropic stiffening in the direction of fiber orientation suggestive of a positive feedback between ECM fiber alignment and forces exerted by cancer cells. Taken together, our findings suggest that the invasive spread of cancer cells can be defined by complex interplay with the surrounding matrix, during which they both modify the matrix and use the matrix alignment as a persistent migration cue, leading to more extensive and rapid invasive spread.

Original languageEnglish (US)
Article number14210
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Melanoma
Neoplasms
Traction
Cell Movement
Cues
Extracellular Matrix
Collagen
Organizations
Morbidity
Mortality
Direction compound

ASJC Scopus subject areas

  • General

Cite this

Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread. / Kim, Deok Ho; Ewald, Andrew; Park, Jin Seok; Kshitiz; Kwak, Moonkyu; Gray, Ryan S.; Su, Chia Yi; Seo, Jayhyun; An, Steven; Levchenko, Andre.

In: Scientific Reports, Vol. 8, No. 1, 14210, 01.12.2018.

Research output: Contribution to journalArticle

Kim, Deok Ho ; Ewald, Andrew ; Park, Jin Seok ; Kshitiz ; Kwak, Moonkyu ; Gray, Ryan S. ; Su, Chia Yi ; Seo, Jayhyun ; An, Steven ; Levchenko, Andre. / Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{0abbde297da44c05aac8b893c2f3f603,
title = "Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread",
abstract = "The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix. When this re-organization is mimicked using a nano-fabricated model of aligned extracellular matrix fibers, metastatic cells, including less invasive melanoma cells, were in turn induced to align, elongate and migrate, guided by the local ridge orientations. Strikingly, we found that this aligned migration of melanoma cells was accompanied by long-range regulation of cytoskeletal remodeling that show anisotropic stiffening in the direction of fiber orientation suggestive of a positive feedback between ECM fiber alignment and forces exerted by cancer cells. Taken together, our findings suggest that the invasive spread of cancer cells can be defined by complex interplay with the surrounding matrix, during which they both modify the matrix and use the matrix alignment as a persistent migration cue, leading to more extensive and rapid invasive spread.",
author = "Kim, {Deok Ho} and Andrew Ewald and Park, {Jin Seok} and Kshitiz and Moonkyu Kwak and Gray, {Ryan S.} and Su, {Chia Yi} and Jayhyun Seo and Steven An and Andre Levchenko",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-32010-3",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread

AU - Kim, Deok Ho

AU - Ewald, Andrew

AU - Park, Jin Seok

AU - Kshitiz,

AU - Kwak, Moonkyu

AU - Gray, Ryan S.

AU - Su, Chia Yi

AU - Seo, Jayhyun

AU - An, Steven

AU - Levchenko, Andre

PY - 2018/12/1

Y1 - 2018/12/1

N2 - The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix. When this re-organization is mimicked using a nano-fabricated model of aligned extracellular matrix fibers, metastatic cells, including less invasive melanoma cells, were in turn induced to align, elongate and migrate, guided by the local ridge orientations. Strikingly, we found that this aligned migration of melanoma cells was accompanied by long-range regulation of cytoskeletal remodeling that show anisotropic stiffening in the direction of fiber orientation suggestive of a positive feedback between ECM fiber alignment and forces exerted by cancer cells. Taken together, our findings suggest that the invasive spread of cancer cells can be defined by complex interplay with the surrounding matrix, during which they both modify the matrix and use the matrix alignment as a persistent migration cue, leading to more extensive and rapid invasive spread.

AB - The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix. When this re-organization is mimicked using a nano-fabricated model of aligned extracellular matrix fibers, metastatic cells, including less invasive melanoma cells, were in turn induced to align, elongate and migrate, guided by the local ridge orientations. Strikingly, we found that this aligned migration of melanoma cells was accompanied by long-range regulation of cytoskeletal remodeling that show anisotropic stiffening in the direction of fiber orientation suggestive of a positive feedback between ECM fiber alignment and forces exerted by cancer cells. Taken together, our findings suggest that the invasive spread of cancer cells can be defined by complex interplay with the surrounding matrix, during which they both modify the matrix and use the matrix alignment as a persistent migration cue, leading to more extensive and rapid invasive spread.

UR - http://www.scopus.com/inward/record.url?scp=85053734393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053734393&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-32010-3

DO - 10.1038/s41598-018-32010-3

M3 - Article

C2 - 30242256

AN - SCOPUS:85053734393

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 14210

ER -