Lipid headgroup and side chain architecture determine manganese-induced dose dependent membrane rigidification and liposome size increase

• Published in: European biophysics journal 2022-04, Vol.51 (3), p.205-223
• Main Authors: Sule, Kevin, Prenner, Elmar J.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Cadmium; Calcium; Cardiolipin; Cell Biology; Cell survival; Fluidity; Fluorescent dyes; Fluorescent indicators; Heavy metals; Homeostasis; Hydrophobicity; Life Sciences; Light scattering; Lipids; Liposomes; Magnesium; Manganese; Membrane Biology; Membrane fluidity; Membrane permeability; Membranes; Metal ions; Mode of action; Nanotechnology; Neurobiology; Original Article; Phase transitions; Phosphatidic acid; Phosphatidylglycerol; Phosphatidylserine; Phospholipids; Photon correlation spectroscopy; Rigidity; Trace metals; Transition temperature; Transition temperatures
• ISSN: 0175-7571; 1432-1017
• DOI: 10.1007/s00249-022-01589-x

Metal ion-membrane interactions have gained appreciable attention over the years resulting in increasing investigations into the mode of action of toxic and essential metals. More work has focused on essential ions like Ca or Mg and toxic metals like Cd and Pb, whereas this study investigates the effects of the abundant essential trace metal manganese with model lipid systems by screening zwitterionic and anionic glycerophospholipids. Despite its essentiality, deleterious impact towards cell survival is known under Mn stress. The fluorescent dyes Laurdan and diphenylhexatriene were used to assess changes in membrane fluidity both in the head group and hydrophobic core region of the membrane, respectively. Mn-rigidified membranes composed of the anionic phospholipids, phosphatidic acid, phosphatidylglycerol, cardiolipin, and phosphatidylserine. Strong binding resulted in large shifts of the phase transition temperature. The increase was in the order phosphatidylserine > phosphatidylglycerol > cardiolipin, and in all cases, saturated analogues > mono-unsaturated forms. Dynamic light scattering measurements revealed that Mn caused extensive aggregation of liposomes composed of saturated analogues of phosphatidic acid and phosphatidylserine, whilst the mono-unsaturated analogue had significant membrane swelling. Increased membrane rigidity may interfere with permeability of ions and small molecules, possibly disrupting cellular homeostasis. Moreover, liposome size changes could indicate fusion, which could also be detrimental to cellular transport. Overall, this study provided further understanding into the effects of Mn with biomembranes, whereby the altered membrane properties are consequential to the proper structural and signalling functions of membrane lipids.