Glycosylphosphatidylinositol-anchored proteins as non-DNA matter of inheritance: from molecular to cell to philosophical biology

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are cell surface proteins attached to the outer leaflet of eukaryotic plasma membranes (PMs) by a covalently attached GPI. Some GPI-APs may be released extracellularly in response to certain stimuli, such as a high-fat diet, leading to their presence in interstitial spaces or the bloodstream, with their GPI anchor remaining intact. This is accomplished by incorporation of GPI fatty acids into the outer phospholipid monolayer of extracellular vesicles (EVs) or alternatively, together with (lyso)phospholipids and cholesterol into micelle-like complexes. The transfer of released full-length GPI-APs via micelle-like complexes or EVs from donor to acceptor cells, either within the same or distant tissue, is known to have functional consequences, such as the stimulation of glycogen and lipid synthesis. This article explores the possibility that the intercellular transfer of GPI-APs via EVs or micelle-like complexes mediates a form of biological inheritance of non-DNA matter. This novel paradigm may be summarized as follows: (i) donor cells not only transfer DNA to acceptor cells but also GPI-APs, transmembrane proteins, and cytoskeletal elements, which constitute the so-called membrane environment landscapes (MELs), via EVs or micelle-like complexes. (ii) The transferred MLs, such as protuberances and invaginations, are replicated by self-organization and amenable to topological changes in response to environmental factors. (iii) Transfer of MELs induces novel phenotypes in acceptor cells. (iv) This transfer of non-DNA matter is understood as epigenetic mechanism for phenotypic plasticity and the inheritance of acquired traits. (v) The reasons for the missing consideration of non-DNA matter in heredity research should become the subject of future studies in the philosophy of biology, in general, and science and technology studies, in particular.