Interactions between antimicrobial polynorbornenes and phospholipid vesicles monitored by light scattering and microcalorimetry.
Antimicrobial polynorbornenes composed of facially amphiphilic monomers have been previously reported to accurately emulate the antimicrobial activity of natural host-defense peptides (HDPs). The lethal mechanism of most HDPs involves binding to the membrane surface of bacteria leading to compromised phospholipid bilayers. In this paper, the interactions between biomimetic vesicle membranes and these cationic antimicrobial polynorbornenes are reported. Vesicle dye-leakage experiments were consistent with previous biological assays and corroborated a mode of action involving membrane disruption. Dynamic light scattering (DLS) showed that these antimicrobial polymers cause extensive aggregation of vesicles without complete bilayer disintegration as observed with surfactants that efficiently solubilize the membrane. Fluorescence microscopy on vesicles and bacterial cells also showed polymer-induced aggregation of both synthetic vesicles and bacterial cells. Isothermal titration calorimetry (ITC) afforded free energy of binding values (Delta G) and polymer to lipid binding ratios, plus revealed that the interaction is entropically favorable (Delta S>0, Delta H>0). It was observed that the strength of vesicle binding was similar between the active polymers while the binding stoichiometries were dramatically different.
Gabriel
Gregory J
GJ
Department of Polymer Science and Engineering, University of Massachusetts, Amherst, MA 01003, USA.
Pool
Joanna G
JG
Som
Abhigyan
A
Dabkowski
Jeffrey M
JM
Coughlin
E Bryan
EB
Muthukumar
M
M
Tew
Gregory N
GN
D000890:Anti-Infective Agents / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods*; D008027:Light; D008856:Microscopy, Fluorescence; D010743:Phospholipids / Q000737:chemistry*; D010969:Plastics / Q000737:chemistry*; D012542:Scattering, Radiation
D000890:Anti-Infective Agents; D010743:Phospholipids; D010969:Plastics; C071464:polynorbornen