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* Cellular Neurobiology Laboratory, Brain and Mind Institute,
Global Health Institute,
Institute of Theoretical Physics, and
Institute of Physics of Complex Matter, École Polytechnique Fédérale de Lausanne, Switzerland; ¶ Biology Institute, Pasteur Institute, Lille, France; and ** Département de Biologie Cellulaire et de Morphologie, Université de Lausanne, Switzerland
Correspondence: Address reprint requests to Sandor Kasas, E-mail: sandor.kasas{at}epfl.ch.
Many approaches have been developed to characterize the heterogeneity of membranes in living cells. In this study, the elastic properties of specific membrane domains in living cells are characterized by atomic force microscopy. Our data reveal the existence of heterogeneous nanometric scale domains with specific biophysical properties. We focused on glycosylphosphatidylinositol (GPI)-anchored proteins, which play an important role in membrane trafficking and cell signaling under both physiological and pathological conditions and which are known to partition preferentially into cholesterol-rich microdomains. We demonstrate that these GPI-anchored proteins reside within domains that are stiffer than the surrounding membrane. In contrast, membrane domains containing the transferrin receptor, which does not associate with cholesterol-rich regions, manifest no such feature. The heightened stiffness of GPI domains is consistent with existing data relating to the specific condensation of lipids and the slow diffusion rates of lipids and proteins therein. Our quantitative data may forge the way to unveiling the links that exist between membrane stiffness, molecular diffusion, and signaling activation.
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