Maintaining integrity of the plasma membrane is essential for cell life. Thus, efficient cell membrane repair mechanisms are crucial for handling membrane disruptions resulting from external perturbations of eukaryotic cells. Cancer cells experience enhanced membrane stress when navigating through the dense extracellular matrix, which increases the frequency of membrane injuries. Yet the underlying molecular details of plasma membrane repair are not well understood. Plasma membrane injury followed by Ca2+ influx, activates the recruitment of Annexins to membrane wound edges. In cancer cells subjected to localized laser damage, we find that binding of several annexin members promotes the repair of lesions. In a planar model membrane system consisting of round membrane patches, we show that curvature stress induced by Annexin A4 leads to roll-up of the membrane as initiated from free membrane edges. The rolling process is deduced by analysis of time-lapse fluorescence images, combined with AFM on the same sample region. We have characterized the effect of 9 human annexins on membranes and shown that they induce distinct morphologies which can all be attributed to curvature. The observation of rolling identifies membrane curvature near hole-edges as a potential key event in the plasma membrane repair (PMR) process. In the geometry of a membrane hole we propose that spontaneous curvature coupled with line tension leads to the formation of a characteristic neck structure around the hole as the first step in the repair process. Formation of a neck geometry is further supported by theoretical modeling.

Annexins induce membrane curvature near hole edges during plasma membrane repair

2019 Spring National Meeting

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