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A Functional Role for N‐cadherin in Mediating Mechanotransduction in Arteriolar Vascular Smooth Muscle Cells
Author(s) -
sun zhe,
Li Zhaohui,
Meininger Gerald A.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.676.7
Subject(s) - mechanotransduction , cadherin , rhoa , myosin , adherens junction , biophysics , vascular smooth muscle , chemistry , microbiology and biotechnology , anatomy , nanotechnology , materials science , cell , smooth muscle , biochemistry , signal transduction , biology , medicine
A hybrid atomic force (AFM)‐confocal microscopy system was used to examine whether mechanical forces applied through N‐cadherin adhesions on vascular smooth muscle cells (VSMC) could induce i) cellular contraction and ii) signaling events. AFM probes were modified by attaching a borosilicate microsphere (5 μm) to the tip and coating with either 1) a recombinant N‐cadherin chimera fusion protein (rhNcad), or 2) an N‐cadherin antibody; or 3) attaching a live VSMC to the end of the AFM cantilever. In all 3 cases, a strong adhesion was formed between the AFM probe and cell membrane; and AFM pulling forces (~1000 pN) induced a strong VSMC contractile response that pulled the probe oppositely. In addition, clustering of N‐cadherin‐GFP and RhoA‐GFP was observed when an rhNcad coated AFM probe was engaged on the VSMC membrane, and application of AFM pulling force enhanced the clustering. Immuno‐fluorescence labeling showed a dramatic increase of N‐cadherin clustering in the vessel wall of pressurized arterioles that developed spontaneous myogenic tone compared to unpressurized vessels, as well as spatial correlations between the N‐cadherin and the clusters of active RhoA, myosin II and the phosphorylated myosin phosphatase targeting subunit. Collectively, these results support an important role for N‐cadherin in mediating the myogenic mechanotransduction in VSMC. (AHA 0835676N to Z.S. and NIH P01HL095486 to G.A.M.)