FRAGMENTATION OF LIPOSOMES BY HYDROPHOBICALLY-MODIFIED POLYPEPTOIDS: ELUCIDATING THE ROLE OF MOLECULAR CHARACTERISTICS

Amphiphiles (e.g. membrane scaffold protein, styrene-co-maleic acid, etc.) stabilized lipid nanodiscs have been developed as water-soluble membrane mimetic platforms to stabilize membrane proteins for further structural characterizations. In contrast to detergent micelles, the structures of membrane proteins in nanodiscs are better retained with enhanced long-term stabilities.
In this work, hydrophobically modified polypeptoids (HMPs) have been designed and investigated as facially amphiphiles to fragment liposome to form stable HMP-lipid complexes or nanodiscs. The effects of polymer concentration, chain length, and relative hydrophobicity on liposome fragmentation have been elucidated by a combination of DLS, SLS and EM analysis. It was found that HMPs with relatively higher polymer hydrophobicity (De mol % = 27 %) and longer chain length (DP_n =100) can induce more effective liposome fragmentation relative to short polymers (DP_n = 34-60) and hydrophilic polymers with similar chain length (DP_n = 96 with De mol % = 16 %). It is hypothesized that a high local hydrophobic contact between polymers and lipid membranes is critical to accelerate and enhance the extent of liposome fragmentation.