Insulin-mediated fusion of negatively charged phospholipid vesicles at low pH

Mechanisms of gene transfer mediated by lipoplexes associated with targeting ligands or pH-sensitive peptides

“…In addition, we can speculate that upon acidification, Tf would acquire fusigenic properties that could also contribute to the destabilization of the endosome, analogous to membrane destabilization and fusion induced at low pH by insulin, clathrin or various colicins. [50][51][52] Thus, besides its major role in triggering both receptor-and non-receptor-mediated endocytosis, Tf may also be involved in overcoming the endosomal membrane barrier to gene transfer. This suggestion is in agreement with the observation that the association of Tf with lipofectin increased DNA entry by only two-fold, while transfection activity was enhanced by a much larger factor.…”

Relationship between isoelectric point of native and chemically modified insulin and liposomal fusion

“…Due to the complexity of biological membranes, the fusion process was mainly studied in membrane model systems, more amenable to experimental analysis, such as liposomes. In this latter system, peptides and proteins were shown to be efficient fusion inducers and were postulated as 'fusogenic agents' of biological relevance [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Also, the molecular mechanism of liposome fusion is still poorly understood.…”

“…Fusion of liposomes modulated by proteins can be generalized as either Ca2"-dependent or Ca2"-independent (see [17] for a review). Recently our laboratory has demonstrated the fusogenic ability of several proteins in the absence of Ca2" [12][13][14][15]. One of these, insulin, can induce fusion of negatively charged small unilamellar vesicles at low pH, but not at neutral pH [13,14].…”

“…Recently our laboratory has demonstrated the fusogenic ability of several proteins in the absence of Ca2" [12][13][14][15]. One of these, insulin, can induce fusion of negatively charged small unilamellar vesicles at low pH, but not at neutral pH [13,14]. Four different procedures were used in support of this conclusion: resonance energy transfer, light scattering, Sepharose chromatography and electron microscopy [13,14].…”

“…One of these, insulin, can induce fusion of negatively charged small unilamellar vesicles at low pH, but not at neutral pH [13,14]. Four different procedures were used in support of this conclusion: resonance energy transfer, light scattering, Sepharose chromatography and electron microscopy [13,14]. This fusion process was inhibited by high salt concentration.…”