TY - JOUR
T1 - Membrane interactions and lipid binding of casein oligomers and early aggregates
AU - Sokolovski, Miri
AU - Sheynis, Tania
AU - Kolusheva, Sofiya
AU - Jelinek, Raz
N1 - Funding Information:
RJ is grateful for the German-Israel DIP foundation for the generous financial support. We are also grateful to Yona Lichtenfeld and Rina Eren Jeger for their assistance with the TEM experiments.
PY - 2008/10/1
Y1 - 2008/10/1
N2 - Caseins constitute the main protein components in mammalian milk and have critical functions in calcium transport and prevention of protein aggregation. Fibrillation and aggregation of κ-casein, a phenomenon which has only recently been detected, might be associated with malfunctions of milk secretion and amyloidosis phenomena in the mammary glands. This study employs a newly-designed chromatic biomimetic vesicle assay to investigate the occurrence and the parameters affecting membrane interactions of casein aggregates and the contribution of individual casein members to membrane binding. We show that physiological casein colloids exhibit membrane activity, as well as early globular aggregates of κ-casein, a prominent casein isoform. Furthermore, inhibition of κ-casein fibrillation through complexation with αS-casein and β-casein, respectively, was found to go hand in hand with induction of enhanced membrane binding; these data are important in the context of casein biology since in secreted milk κ-casein is found only in assemblies containing also αS-casein and β-casein. The chromatic experiments, complemented by transmission electron microscopy analysis and fluorescence quenching assays, also revealed significantly higher affinity early spherical aggregates of k-casein to anionic phosphatidylglycerol-lipids, as compared to zwitterionic phospholipids. Overall, this study suggests that lipid interactions play important roles in maintaining the essential physiological functions of caseins in mammalian milk.
AB - Caseins constitute the main protein components in mammalian milk and have critical functions in calcium transport and prevention of protein aggregation. Fibrillation and aggregation of κ-casein, a phenomenon which has only recently been detected, might be associated with malfunctions of milk secretion and amyloidosis phenomena in the mammary glands. This study employs a newly-designed chromatic biomimetic vesicle assay to investigate the occurrence and the parameters affecting membrane interactions of casein aggregates and the contribution of individual casein members to membrane binding. We show that physiological casein colloids exhibit membrane activity, as well as early globular aggregates of κ-casein, a prominent casein isoform. Furthermore, inhibition of κ-casein fibrillation through complexation with αS-casein and β-casein, respectively, was found to go hand in hand with induction of enhanced membrane binding; these data are important in the context of casein biology since in secreted milk κ-casein is found only in assemblies containing also αS-casein and β-casein. The chromatic experiments, complemented by transmission electron microscopy analysis and fluorescence quenching assays, also revealed significantly higher affinity early spherical aggregates of k-casein to anionic phosphatidylglycerol-lipids, as compared to zwitterionic phospholipids. Overall, this study suggests that lipid interactions play important roles in maintaining the essential physiological functions of caseins in mammalian milk.
KW - Amyloidogenic protein
KW - Casein
KW - Casein fibrils
KW - Membrane interaction
KW - Polydiacetylene
KW - Pre-fibril oligomers
UR - http://www.scopus.com/inward/record.url?scp=52049088512&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2008.07.001
DO - 10.1016/j.bbamem.2008.07.001
M3 - Article
AN - SCOPUS:52049088512
SN - 0005-2736
VL - 1778
SP - 2341
EP - 2349
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 10
ER -