TY - JOUR
T1 - Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments
AU - Wisdom, Katrina M.
AU - Adebowale, Kolade
AU - Chang, Julie
AU - Lee, Joanna Y.
AU - Nam, Sungmin
AU - Desai, Rajiv
AU - Rossen, Ninna Struck
AU - Rafat, Marjan
AU - West, Robert B.
AU - Hodgson, Louis
AU - Chaudhuri, Ovijit
N1 - Funding Information:
We acknowledge Ryan Stowers in the Chaudhuri lab for discussions and technical assistance, David Mooney (Harvard University) for helpful discussions, and Marc Levenston (Stanford University) for use of mechanical testing equipment. We also acknowledge the Stanford Cell Sciences Imaging Facility for software access (Imaris) and the Stanford Statistics Department for their consulting services. This work was supported by National Science Foundation Graduate Research Fellowships to K.M.W. and K.A., a Stanford University Vice Provost for Graduate Education Diversifying Academia and Recruiting Excellence (DARE) Fellowship to K.M.W., a Robert and Marvel Kirby Stanford Graduate Fellowship and Stanford ChEM-H Chemistry/Biology Interface Predoctoral Training Program to K.A., a National Defense Science and Engineering Graduate Fellowship (NDSEG) to J.C., a Samsung Scholarship to S.N., a Novo Nordisk Foundation Visiting Scholar Fellowship at Stanford Bio-X (NNF15OC0015218) for N.S. R, National Institutes of Health grants (CA205262, GM129098) for L.H. and (K99CA201304) for M.R., and an American Cancer Society grant (RSG-16-028-01) and a National Institutes of Health National Cancer Institute Grant (R37 CA214136) for O.C.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Studies of cancer cell migration have found two modes: one that is protease-independent, requiring micron-sized pores or channels for cells to squeeze through, and one that is protease-dependent, relevant for confining nanoporous matrices such as basement membranes (BMs). However, many extracellular matrices exhibit viscoelasticity and mechanical plasticity, irreversibly deforming in response to force, so that pore size may be malleable. Here we report the impact of matrix plasticity on migration. We develop nanoporous and BM ligand-presenting interpenetrating network (IPN) hydrogels in which plasticity could be modulated independent of stiffness. Strikingly, cells in high plasticity IPNs carry out protease-independent migration through the IPNs. Mechanistically, cells in high plasticity IPNs extend invadopodia protrusions to mechanically and plastically open up micron-sized channels and then migrate through them. These findings uncover a new mode of protease-independent migration, in which cells can migrate through confining matrix if it exhibits sufficient mechanical plasticity.
AB - Studies of cancer cell migration have found two modes: one that is protease-independent, requiring micron-sized pores or channels for cells to squeeze through, and one that is protease-dependent, relevant for confining nanoporous matrices such as basement membranes (BMs). However, many extracellular matrices exhibit viscoelasticity and mechanical plasticity, irreversibly deforming in response to force, so that pore size may be malleable. Here we report the impact of matrix plasticity on migration. We develop nanoporous and BM ligand-presenting interpenetrating network (IPN) hydrogels in which plasticity could be modulated independent of stiffness. Strikingly, cells in high plasticity IPNs carry out protease-independent migration through the IPNs. Mechanistically, cells in high plasticity IPNs extend invadopodia protrusions to mechanically and plastically open up micron-sized channels and then migrate through them. These findings uncover a new mode of protease-independent migration, in which cells can migrate through confining matrix if it exhibits sufficient mechanical plasticity.
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U2 - 10.1038/s41467-018-06641-z
DO - 10.1038/s41467-018-06641-z
M3 - Article
C2 - 30297715
AN - SCOPUS:85054563105
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4144
ER -
