TY - JOUR
T1 - 3D Columnar Phase of Stacked Short DNA Organized by Coherent Membrane Undulations
AU - Bouxsein, Nathan F.
AU - Leal, Cecília
AU - McAllister, Christopher S.
AU - Li, Youli
AU - Ewert, Kai K.
AU - Samuel, Charles E.
AU - Safinya, Cyrus R.
N1 - Funding Information:
This work was primarily supported by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Award No. DE-FG02-06ER46314 (self- and directed assembly in charged biomolecular materials systems). Partial support was further provided by the U.S. National Science Foundation (NSF) under Award No. DMR-1807327 (membrane phase behavior) and the by the U.S. National Institutes of Health (NIH) under Award No. R01GM130769 (efficient packing of small nucleic acids in cationic liposome vectors for delivery applications). C.L. was supported by NSF-DMR 1554435 and NIH-1DP2EB024377-01. C.E.S. and C.S.M. were supported by NIH RO1AI020611. The research reported here made use of shared experimental facilities of the Materials Research Laboratory at UCSB: an NSF MRSEC (supported by NSF DMR 1720256) and a member of the NSF-supported Materials Research Facilities Network ( www.mrfn.org ). The X-ray diffraction work was carried out at the Stanford Synchrotron Radiation Lightsource, a Directorate of SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the U.S. DOE Office of Science by Stanford University.
Funding Information:
This work was primarily supported by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Award No. DEFG02-06ER46314 (self- and directed assembly in charged biomolecular materials systems). Partial support was further provided by the U.S. National Science Foundation (NSF) under Award No. DMR-1807327 (membrane phase behavior) and the by the U.S. National Institutes of Health (NIH) under Award No. R01GM130769 (efficient packing of small nucleic acids in cationic liposome vectors for delivery applications). C.L. was supported by NSF-DMR 1554435 and NIH- 1DP2EB024377-01. C.E.S. and C.S.M. were supported by NIH RO1AI020611. The research reported here made use of shared experimental facilities of the Materials Research Laboratory at UCSB: an NSF MRSEC (supported by NSF DMR 1720256) and a member of the NSF-supported Materials Research Facilities Network (www.mrfn.org). The X-ray diffraction work was carried out at the Stanford Synchrotron Radiation Lightsource, a Directorate of SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the U.S. DOE Office of Science by Stanford University.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/9/10
Y1 - 2019/9/10
N2 - We report on the discovery of a new organized lipid-nucleic acid phase upon intercalation of blunt duplexes of short DNA (sDNA) within cationic multilayer fluid membranes. End-to-end interactions between sDNA leads to columnar stacks. At high membrane charge density, with the inter-sDNA column spacing (dsDNA) comparable but larger than the diameter of sDNA, a 2D columnar phase (i.e., a 2D smectic) is found similar to the phase in cationic liposome-DNA complexes with long lambda-phage DNA. Remarkably, with increasing dsDNA as the membrane charge density is lowered, a transition is observed to a 3D columnar phase of stacked sDNA. This occurs even though direct DNA-DNA electrostatic interactions across layers are screened by diffusing cationic lipids near the phosphate groups of sDNA. Softening of the membrane bending rigidity (κ), which further promotes membrane undulations, significantly enhances the 3D columnar phase. These observations are consistent with a model by Schiessel and Aranda-Espinoza where local membrane undulations, due to electrostatically induced membrane wrapping around sDNA columns, phase lock from layer-to-layer, thereby precipitating coherent "crystal-like" undulations coupled to sDNA columns with long-range position and orientation order. The finding that this new phase is stable at large dsDNA and enhanced with decreasing κ is further supportive of the model where the elastic cost of membrane deformation per unit area around sDNA columns (∈ κh2/dsDNA 4, h2 = sum of square of amplitudes of the inner and outer monolayer undulations) is strongly reduced relative to the favorable electrostatic attractions of partially wrapped membrane around sDNA columns. The findings have broad implications in the design of membrane-mediated assembly of functional nanoparticles in 3D.
AB - We report on the discovery of a new organized lipid-nucleic acid phase upon intercalation of blunt duplexes of short DNA (sDNA) within cationic multilayer fluid membranes. End-to-end interactions between sDNA leads to columnar stacks. At high membrane charge density, with the inter-sDNA column spacing (dsDNA) comparable but larger than the diameter of sDNA, a 2D columnar phase (i.e., a 2D smectic) is found similar to the phase in cationic liposome-DNA complexes with long lambda-phage DNA. Remarkably, with increasing dsDNA as the membrane charge density is lowered, a transition is observed to a 3D columnar phase of stacked sDNA. This occurs even though direct DNA-DNA electrostatic interactions across layers are screened by diffusing cationic lipids near the phosphate groups of sDNA. Softening of the membrane bending rigidity (κ), which further promotes membrane undulations, significantly enhances the 3D columnar phase. These observations are consistent with a model by Schiessel and Aranda-Espinoza where local membrane undulations, due to electrostatically induced membrane wrapping around sDNA columns, phase lock from layer-to-layer, thereby precipitating coherent "crystal-like" undulations coupled to sDNA columns with long-range position and orientation order. The finding that this new phase is stable at large dsDNA and enhanced with decreasing κ is further supportive of the model where the elastic cost of membrane deformation per unit area around sDNA columns (∈ κh2/dsDNA 4, h2 = sum of square of amplitudes of the inner and outer monolayer undulations) is strongly reduced relative to the favorable electrostatic attractions of partially wrapped membrane around sDNA columns. The findings have broad implications in the design of membrane-mediated assembly of functional nanoparticles in 3D.
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U2 - 10.1021/acs.langmuir.9b01726
DO - 10.1021/acs.langmuir.9b01726
M3 - Article
C2 - 31408350
AN - SCOPUS:85071999480
SN - 0743-7463
VL - 35
SP - 11891
EP - 11901
JO - Langmuir
JF - Langmuir
IS - 36
ER -