Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation

Neil M. Neumann, Matthew C. Perrone, Jim H. Veldhuis, Robert J. Huebner, Huiwang Zhan, Peter N Devreotes, G. Wayne Brodland, Andrew Ewald

Research output: Contribution to journalArticle

Abstract

We sought to understand how cells collectively elongate epithelial tubes. We first used 3D culture and biosensor imaging to demonstrate that epithelial cells enrich Ras activity, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), and F-actin to their leading edges during migration within tissues. PIP3 enrichment coincided with, and could enrich despite inhibition of, F-actin dynamics, revealing a conserved migratory logic compared with single cells. We discovered that migratory cells can intercalate into the basal tissue surface and contribute to tube elongation. We then connected molecular activities to subcellular mechanics using force inference analysis. Migration and transient intercalation required specific and similar anterior-posterior ratios of interfacial tension. Permanent intercalations were distinguished by their capture at the boundary through time-varying tension dynamics. Finally, we integrated our experimental and computational data to generate a finite element model of tube elongation. Our model revealed that intercalation, interfacial tension dynamics, and high basal stress are together sufficient for mammary morphogenesis. Neumann et al. demonstrate that the spatial asymmetries and molecular logic of migration are conserved between epithelial cells within mammalian tissues and single cells on flat substrates. Force inference techniques and finite element modeling further define a set of mechanical properties and cell behaviors, including radial intercalation, that elongate tubes.

Original languageEnglish (US)
Pages (from-to)67-82.e6
JournalDevelopmental Cell
Volume45
Issue number1
DOIs
StatePublished - Apr 9 2018

Fingerprint

Surface Tension
Receptor Protein-Tyrosine Kinases
Intercalation
Surface tension
Elongation
Tissue
Actins
Epithelial Cells
Biosensors
Biosensing Techniques
Mechanics
Morphogenesis
Imaging techniques
Breast
Mechanical properties
Substrates

Keywords

  • branching morphogenesis
  • cell migration
  • cellular force inference toolkit (CellFIT)
  • epithelial biology
  • finite element modeling
  • interfacial tension
  • mammary gland
  • mechanical signaling
  • radial intercalation

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation. / Neumann, Neil M.; Perrone, Matthew C.; Veldhuis, Jim H.; Huebner, Robert J.; Zhan, Huiwang; Devreotes, Peter N; Brodland, G. Wayne; Ewald, Andrew.

In: Developmental Cell, Vol. 45, No. 1, 09.04.2018, p. 67-82.e6.

Research output: Contribution to journalArticle

Neumann, Neil M. ; Perrone, Matthew C. ; Veldhuis, Jim H. ; Huebner, Robert J. ; Zhan, Huiwang ; Devreotes, Peter N ; Brodland, G. Wayne ; Ewald, Andrew. / Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation. In: Developmental Cell. 2018 ; Vol. 45, No. 1. pp. 67-82.e6.
@article{ea2ea6bea70b4cba87afc769d2ae6770,
title = "Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation",
abstract = "We sought to understand how cells collectively elongate epithelial tubes. We first used 3D culture and biosensor imaging to demonstrate that epithelial cells enrich Ras activity, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), and F-actin to their leading edges during migration within tissues. PIP3 enrichment coincided with, and could enrich despite inhibition of, F-actin dynamics, revealing a conserved migratory logic compared with single cells. We discovered that migratory cells can intercalate into the basal tissue surface and contribute to tube elongation. We then connected molecular activities to subcellular mechanics using force inference analysis. Migration and transient intercalation required specific and similar anterior-posterior ratios of interfacial tension. Permanent intercalations were distinguished by their capture at the boundary through time-varying tension dynamics. Finally, we integrated our experimental and computational data to generate a finite element model of tube elongation. Our model revealed that intercalation, interfacial tension dynamics, and high basal stress are together sufficient for mammary morphogenesis. Neumann et al. demonstrate that the spatial asymmetries and molecular logic of migration are conserved between epithelial cells within mammalian tissues and single cells on flat substrates. Force inference techniques and finite element modeling further define a set of mechanical properties and cell behaviors, including radial intercalation, that elongate tubes.",
keywords = "branching morphogenesis, cell migration, cellular force inference toolkit (CellFIT), epithelial biology, finite element modeling, interfacial tension, mammary gland, mechanical signaling, radial intercalation",
author = "Neumann, {Neil M.} and Perrone, {Matthew C.} and Veldhuis, {Jim H.} and Huebner, {Robert J.} and Huiwang Zhan and Devreotes, {Peter N} and Brodland, {G. Wayne} and Andrew Ewald",
year = "2018",
month = "4",
day = "9",
doi = "10.1016/j.devcel.2018.03.011",
language = "English (US)",
volume = "45",
pages = "67--82.e6",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation

AU - Neumann, Neil M.

AU - Perrone, Matthew C.

AU - Veldhuis, Jim H.

AU - Huebner, Robert J.

AU - Zhan, Huiwang

AU - Devreotes, Peter N

AU - Brodland, G. Wayne

AU - Ewald, Andrew

PY - 2018/4/9

Y1 - 2018/4/9

N2 - We sought to understand how cells collectively elongate epithelial tubes. We first used 3D culture and biosensor imaging to demonstrate that epithelial cells enrich Ras activity, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), and F-actin to their leading edges during migration within tissues. PIP3 enrichment coincided with, and could enrich despite inhibition of, F-actin dynamics, revealing a conserved migratory logic compared with single cells. We discovered that migratory cells can intercalate into the basal tissue surface and contribute to tube elongation. We then connected molecular activities to subcellular mechanics using force inference analysis. Migration and transient intercalation required specific and similar anterior-posterior ratios of interfacial tension. Permanent intercalations were distinguished by their capture at the boundary through time-varying tension dynamics. Finally, we integrated our experimental and computational data to generate a finite element model of tube elongation. Our model revealed that intercalation, interfacial tension dynamics, and high basal stress are together sufficient for mammary morphogenesis. Neumann et al. demonstrate that the spatial asymmetries and molecular logic of migration are conserved between epithelial cells within mammalian tissues and single cells on flat substrates. Force inference techniques and finite element modeling further define a set of mechanical properties and cell behaviors, including radial intercalation, that elongate tubes.

AB - We sought to understand how cells collectively elongate epithelial tubes. We first used 3D culture and biosensor imaging to demonstrate that epithelial cells enrich Ras activity, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), and F-actin to their leading edges during migration within tissues. PIP3 enrichment coincided with, and could enrich despite inhibition of, F-actin dynamics, revealing a conserved migratory logic compared with single cells. We discovered that migratory cells can intercalate into the basal tissue surface and contribute to tube elongation. We then connected molecular activities to subcellular mechanics using force inference analysis. Migration and transient intercalation required specific and similar anterior-posterior ratios of interfacial tension. Permanent intercalations were distinguished by their capture at the boundary through time-varying tension dynamics. Finally, we integrated our experimental and computational data to generate a finite element model of tube elongation. Our model revealed that intercalation, interfacial tension dynamics, and high basal stress are together sufficient for mammary morphogenesis. Neumann et al. demonstrate that the spatial asymmetries and molecular logic of migration are conserved between epithelial cells within mammalian tissues and single cells on flat substrates. Force inference techniques and finite element modeling further define a set of mechanical properties and cell behaviors, including radial intercalation, that elongate tubes.

KW - branching morphogenesis

KW - cell migration

KW - cellular force inference toolkit (CellFIT)

KW - epithelial biology

KW - finite element modeling

KW - interfacial tension

KW - mammary gland

KW - mechanical signaling

KW - radial intercalation

UR - http://www.scopus.com/inward/record.url?scp=85044745234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044745234&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2018.03.011

DO - 10.1016/j.devcel.2018.03.011

M3 - Article

C2 - 29634937

AN - SCOPUS:85044745234

VL - 45

SP - 67-82.e6

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 1

ER -