Development of protein extraction and identification methods from a live cell surface using minimally invasive technology has an important implication as a possible tool to study time-dependent changes of the distribution of intrinsic membrane proteins in specific locals on the cell membrane. We have approached to this problem using an atomic force microscope mounted with a chemically modified probe with amino reactive covalent crosslinkers against amino groups on the membrane proteins. We discuss the probability of protein extraction versus covalent bond rupture in the experimentally observed rupture force in protein extraction. Possibility of protein unfolding by mechanical stretching during extraction from the cell surface is discussed. (C) 2004 Elsevier B.V. All rights reserved.