TY - JOUR
T1 - Mesoscale computer modeling of Lipid-DNA complexes for gene therapy
AU - Farago, Oded
AU - Grønbech-Jensen, Niels
AU - Pincus, Philip
PY - 2006/1/13
Y1 - 2006/1/13
N2 - We report on a molecular simulation method, which captures the self-assembly of cationic lipid-DNA (CL-DNA) gene delivery complexes. Computational efficiency required for large length- and time-scale simulations is achieved through a coarse-grained representation of the intramolecular details and via intermolecular potentials, which effectively mimic the hydrophobic effect without an explicit solvent. The broad utility of the model is illustrated by demonstrating excellent agreement with x-ray diffraction experimental data for the dependence of the spacing between DNA chains on the concentration of CLs. At high concentrations, the large electrostatic pressure induces the formation of pores in the membranes through which the DNA molecules may escape the complex. We relate this observation to the origin of recently observed enhanced transfection efficiency of lamellar CL-DNA complexes at high charge densities.
AB - We report on a molecular simulation method, which captures the self-assembly of cationic lipid-DNA (CL-DNA) gene delivery complexes. Computational efficiency required for large length- and time-scale simulations is achieved through a coarse-grained representation of the intramolecular details and via intermolecular potentials, which effectively mimic the hydrophobic effect without an explicit solvent. The broad utility of the model is illustrated by demonstrating excellent agreement with x-ray diffraction experimental data for the dependence of the spacing between DNA chains on the concentration of CLs. At high concentrations, the large electrostatic pressure induces the formation of pores in the membranes through which the DNA molecules may escape the complex. We relate this observation to the origin of recently observed enhanced transfection efficiency of lamellar CL-DNA complexes at high charge densities.
UR - http://www.scopus.com/inward/record.url?scp=32644460458&partnerID=8YFLogxK
U2 - 10.1103/PhysRevLett.96.018102
DO - 10.1103/PhysRevLett.96.018102
M3 - Article
C2 - 16486522
AN - SCOPUS:32644460458
SN - 0031-9007
VL - 96
JO - Physical Review Letters
JF - Physical Review Letters
IS - 1
M1 - 018102
ER -