Tubulohelical membrane arrays: From the initial observation to the elucidation of nanophysical properties and cellular function

MCS codes: 92C37, 92C05, 92C50Cells have internalized self-assembly of lipid-phase dependent membranes as part of their life-organizing strategy. The diversity of lipid membrane structures has been highlighted by Tresset [1]. Among them, nanoperiodic 3D-arrays, so-called cubic phases, are of particular interest, since they inspire to a technical route to the in vitro-fabrication of 3D structures [2,3]. Whereas engineering of a man-made functional design is envisaged, it is unclear what the purpose of such membrane arrays in living cells might be. Do these arrays make use of physical properties resulting from their nanoarchitecture? Do they act as building blocks for cellular "technologies", yet to be conceived by humans? With next to no knowledge of the function of cellular nanoarrays, addressing such questions is difficult.Here we want to raise the interest of biophysicists in a novel lipid membrane array since this could open prospects for studies of their self-assembly in relation to their cellular function. Initially, we observed this membrane array in the renal epithelial cell line PtK2, processed by state-of-the-art preparation techniques for electron microscopy (EM) [4]. Since it differs from any of the other highly ordered membrane structures reported previously, we named it the "tubulohelical membrane array" (TUHMA).Complex cellular lipid membrane structures and arrays, including those displaying nonlamellar aspects, are visible after conventional chemical fixation with cross-linking aldehydes followed by dehydration and subsequent embedding in epoxy resin. For viewing in the electron microscope, the resulting thin sections of the embedded samples are contrasted with heavy metals. The visibility of the lipid membranes in such preparations relies on the retention of lipids by post-fixation with osmium tetroxide. Accordingly, almost all observation of lipid membranes of higher order, such as organized smooth endoplasmic reticulum (OSER), tubuloreticular struc