Strain matrix-dependently dissociates gut epithelial spreading and motility.
BACKGROUND
Repetitive deformation enhances intestinal epithelial migration across tissue fibronectin (tFN) via Src but inhibits migration across collagen. Since cell spreading generally precedes motility, we compared the effects of cyclic strain on Caco-2 spreading and migration on tFN, collagen-I, and plasma fibronectin (pFN), and investigated the role of Src in deformation-influenced spreading and migration.


METHODS
Human Caco-2 intestinal epithelial cells on tFN, collagen-I or pFN were subjected to an average 10% strain at 10 cycles/min for 2 h. Src was inhibited with 10muM PP2 or Src was reduced with siRNA. Parallel studies assessed deformation effects on monolayer wound closure.


RESULTS
Deformation, Src-inhibition or reduction each inhibited spreading on tFN but Src-inhibition or reduction prevented further inhibition of spreading by deformation without preventing further inhibition of motility. Deformation did not alter spreading on collagen-I or pFN, but inhibited wound closure.


CONCLUSIONS
Although cell spreading generally precedes and parallels motility, repetitive deformation regulates motility independently of spreading. Since deformation activates Src, the ability of Src blockade to mimic strain-associated inhibition of spreading on tFN suggests that this effect occurs by a separate mechanism that may also require basal Src activity. Further delineation of the mechanisms by which strain disparately modulates spreading and motility may permit acceleration of mucosal healing by targeted interventions to separately promote spreading and epithelial motility.
Chaturvedi
Lakshmi S
LS
Department of Surgery, John D. Dingell VA Medical Center, Detroit, Michigan, USA.
Saad
Samira A
SA
Bakshi
Neil
N
Marsh
Harold M
HM
Basson
Marc D
MD
D018938:Caco-2 Cells; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D024042:Collagen Type I / Q000494:pharmacology; D005109:Extracellular Matrix / Q000737:chemistry / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction; D013314:Stress, Mechanical; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D024042:Collagen Type I; D005353:Fibronectins; D034741:RNA, Small Interfering; D019061:src-Family Kinases
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