title: Poly(amidoamine) dendrimers on lipid bilayers I: Free energy and conformation of binding.
abstract: Third-generation (G3) poly(amidoamine) (PAMAM) dendrimers are simulated approaching 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) bilayers with fully atomistic molecular dynamics, which enables the calculation of a free energy profile along the approach coordinate. Three different dendrimer terminations are examined: protonated primary amine, uncharged acetamide, and deprotonated carboxylic acid. As the dendrimer and lipids become closer, their attractive force increases (up to 240 pN) and the dendrimer becomes deformed as it interacts with the lipids. The total energy release upon binding of a G3-NH3+, G3-Ac, or G3-COO- dendrimer to a DMPC bilayer is, respectively, 36, 26, or 47 kcal/mol or, equivalently, 5.2, 3.2, or 4.7x10(-3) kcal/g. These results are analyzed in terms of the dendrimers' size, shape, and atomic distributions as well as proximity of individual lipid molecules and particular lipid atoms to the dendrimer. For example, an area of 9.6, 8.2, or 7.9 nm2 is covered on the bilayer for the G3-NH3+, G3-Ac, or G3-COO- dendrimers, respectively, while interacting strongly with 18-13 individual lipid molecules.
authors.affiliation: Applied Physics Program, Biophysics, Graham Environmental Sustainability Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Kelly
authors.forename: Pascale R
authors.initials: PR
authors.lastname: Leroueil
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Nett
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Wereszczynski
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Orr
authors.forename: Mark M
authors.initials: MM
authors.lastname: Banaszak Holl
authors.forename: Ioan
authors.initials: I
authors.lastname: Andricioaei
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D008051:Lipid Bilayers; C531249:Poly(amidoamine); D011073:Polyamines; D004134:Dimyristoylphosphatidylcholine