Anisotropy of cell adhesive microenvironment governs cell internal organization and orientation of polarity
Proc Natl Acad Sci U S A.. 2006 Dec 26; 103(52): 19771-6
DOI: 0609267103 [pii]10.1073/pnas.0609267103
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Control of the establishment of cell polarity is an essential function in tissue
morphogenesis and renewal that depends on spatial cues provided by the
extracellular environment. The molecular role of cell-cell or cell-extracellular
matrix (ECM) contacts on the establishment of cell polarity has been well
characterized. It has been hypothesized that the geometry of the cell adhesive
microenvironment was directing cell surface polarization and internal
organization. To define how the extracellular environment affects cell polarity,
we analyzed the organization of individual cells plated on defined micropatterned
substrates imposing cells to spread on various combinations of adhesive and
nonadhesive areas. The reproducible normalization effect on overall cell
compartmentalization enabled quantification of the spatial organization of the
actin network and associated proteins, the spatial distribution of microtubules,
and the positioning of nucleus, centrosome, and Golgi apparatus. By using
specific micropatterns and statistical analysis of cell compartment positions, we
demonstrated that ECM geometry determines the orientation of cell polarity axes.
The nucleus-centrosome orientations were reproducibly directed toward cell
adhesive edges. The anisotropy of the cell cortex in response to the adhesive
conditions did not affect the centrosome positioning at the cell centroid. Based
on the quantification of microtubule plus end distribution we propose a working
model that accounts for that observation. We conclude that, in addition to
molecular composition and mechanical properties, ECM geometry plays a key role in
developmental processes.
DOI: 10.1073/pnas.0609267103
PMCID: PMC1750916
PMID: 17179050 [Indexed for MEDLINE]