Title: Assembly of Building Blocks by Double-End-Anchored Polymers in the Dilute Regime Mediated by Hydrophobic Interactions at Controlled Distances

Abstract

Hierarchical assembly of building blocks via competing, orthogonal interactions is a hallmark of many of nature’s composite materials that do not require highly specific ligand-receptor interactions. To mimic this assembly mechanism requires the development of building blocks capable of tunable interactions. In the present work, we explored the interplay between repulsive (steric and electrostatic) and attractive hydrophobic forces. The designed building blocks allow hydrophobic forces to effectively act at controlled, large distances, to create and tune the assembly of membrane-based building blocks under dilute conditions and affect their interactions with cellular membranes via physical cross-bridges. Specifically, we employed double-end-anchored poly(ethylene glycol)s (DEA-PEGs)—hydrophilic PEG tethers with hydrophobic tails on both ends. Using differential-interference-contrast optical microscopy, synchrotron small angle X-ray scattering (SAXS), and cryogenic electron microscopy, we investigated the ability of DEA-PEGs to mediate assembly in the dilute regime on multiple length scales and on practical time scales. The PEG length, anchor hydrophobicity, and molar fraction of DEA-PEG molecules within a membrane strongly affect the assembly properties. Additional tuning of the intermembrane interactions can be achieved by adding repulsive interactions via PEG-lipids (steric) or cationic lipids to the DEA-PEG-mediated attractions. Further, while the optical and electron microscope imaging methods provided qualitative evidencemore » of the ability of DEA-PEGs to assemble liposomes, the SAXS measurements and quantitative line-shape analysis in dilute preparations demonstrated that the ensemble average of loosely organized liposomal assemblies maintains DEA-PEG concentration-dependent tethering on defined nanometer length scales. For cationic liposome–DNA nanoparticles (CL–DNA NPs), aggregation induced by DEA-PEGs decreased internalization of NPs by cells, but tuning the DEA-PEG-induced attractions by adding repulsive steric interactions via PEG-lipids limited aggregation and increased NP uptake. However, confocal microscopy imaging together with colocalization studies with Rab11 and LysoTracker as markers of intracellular pathways showed that modifying CL–DNA NPs with DEA-PEGs alters their interactions with the plasma and endosomal membranes.« less

Authors:

Wonder, Emily A.  ^[1];

• Search DOE PAGES for author "Wonder, Emily A."
• Search DOE PAGES for ORCID "0000-0001-8704-0096"

Ewert, Kai K.  ^[1];

• Search DOE PAGES for author "Ewert, Kai K."
• Search DOE PAGES for ORCID "0000-0002-4861-8278"

Liu, Chenyu  ^[2];

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• Search DOE PAGES for ORCID "0000-0002-9164-6733"

Steffes, Victoria M.  ^[1];

• Search DOE PAGES for author "Steffes, Victoria M."
• Search DOE PAGES for ORCID "0000-0002-5665-1131"

Kwak, Jasmin ^[1]; Qahar, Vikar ^[1]; Majzoub, Ramsey N. ^[1]; Zhang, Zhening ^[3]; Carragher, Bridget ^[3]; Potter, Clinton S. ^[3]; Li, Youli  ^[1];

• Search DOE PAGES for author "Li, Youli"
• Search DOE PAGES for ORCID "0000-0001-5117-3874"

Qiao, Weihong  ^[4];

• Search DOE PAGES for author "Qiao, Weihong"
• Search DOE PAGES for ORCID "0000-0003-4007-7494"

Safinya, Cyrus R.  ^[1]

• Search DOE PAGES for author "Safinya, Cyrus R."
• Search DOE PAGES for ORCID "0000-0002-3295-7128"

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+ Show Author Affiliations

1. Univ. of California, Santa Barbara, CA (United States)
2. Univ. of California, Santa Barbara, CA (United States); Dalian Univ. of Technology (China)
3. New York Structural Biology Center, NY (United States)
4. Dalian Univ. of Technology (China)

Publication Date:

Tue Sep 22 00:00:00 EDT 2020

Research Org.:

Univ. of California, Santa Barbara, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division; National Science Foundation (NSF); National Institutes of Health (NIH); Simons Foundation; National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:

1763432

Alternate Identifier(s):

OSTI ID: 1908362

Grant/Contract Number:  

FG02-06ER46314; DGE 1144085; R01GM130769; DMR-1807327; SF349247; GM103310

Resource Type:

Accepted Manuscript

Journal Name:

ACS Applied Materials and Interfaces

Additional Journal Information:

Journal Volume: 12; Journal Issue: 41; Journal ID: ISSN 1944-8244

Publisher:

American Chemical Society (ACS)

Country of Publication:

United States

Language:

English

Subject:

36 MATERIALS SCIENCE; PEG-lipid; liposomes; self-assembly; hydrophobic-mediated tethering; tunable assembly; competing interactions; lipid membrane; lipid bilayer; vesicles; lipids; - x-ray scattering; membranes; chemical structure