skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Efficient encapsulation of proteins with random copolymers

Abstract

Membraneless organelles are aggregates of disordered proteins that form spontaneously to promote specific cellular functions in vivo. The possibility of synthesizing membraneless organelles out of cells will therefore enable fabrication of protein-based materials with functions inherent to biological matter. Since random copolymers contain various compositions and sequences of solvophobic and solvophilic groups, they are expected to function in nonbiological media similarly to a set of disordered proteins in membraneless organelles. Interestingly, the internal environment of these organelles has been noted to behave more like an organic solvent than like water. Therefore, an adsorbed layer of random copolymers that mimics the function of disordered proteins could, in principle, protect and enhance the proteins’ enzymatic activity even in organic solvents, which are ideal when the products and/or the reactants have limited solubility in aqueous media. Here, we demonstrate via multiscale simulations that random copolymers efficiently incorporate proteins into different solvents with the potential to optimize their enzymatic activity. We investigate the key factors that govern the ability of random copolymers to encapsulate proteins, including the adsorption energy, copolymer average composition, and solvent selectivity. The adsorbed polymer chains have remarkably similar sequences, indicating that the proteins are able to select certain sequences thatmore » best reduce their exposure to the solvent. We also find that the protein surface coverage decreases when the fluctuation in the average distance between the protein adsorption sites increases. The results herein set the stage for computational design of random copolymers for stabilizing and delivering proteins across multiple media.« less

Authors:
ORCiD logo; ;
Publication Date:
Research Org.:
Northwestern Univ., Evanston, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1441241
Alternate Identifier(s):
OSTI ID: 1540300
Grant/Contract Number:  
FG02-08ER46539
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 26; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Nguyen, Trung Dac, Qiao, Baofu, and Olvera de la Cruz, Monica. Efficient encapsulation of proteins with random copolymers. United States: N. p., 2018. Web. doi:10.1073/pnas.1806207115.
Nguyen, Trung Dac, Qiao, Baofu, & Olvera de la Cruz, Monica. Efficient encapsulation of proteins with random copolymers. United States. doi:10.1073/pnas.1806207115.
Nguyen, Trung Dac, Qiao, Baofu, and Olvera de la Cruz, Monica. Tue . "Efficient encapsulation of proteins with random copolymers". United States. doi:10.1073/pnas.1806207115.
@article{osti_1441241,
title = {Efficient encapsulation of proteins with random copolymers},
author = {Nguyen, Trung Dac and Qiao, Baofu and Olvera de la Cruz, Monica},
abstractNote = {Membraneless organelles are aggregates of disordered proteins that form spontaneously to promote specific cellular functions in vivo. The possibility of synthesizing membraneless organelles out of cells will therefore enable fabrication of protein-based materials with functions inherent to biological matter. Since random copolymers contain various compositions and sequences of solvophobic and solvophilic groups, they are expected to function in nonbiological media similarly to a set of disordered proteins in membraneless organelles. Interestingly, the internal environment of these organelles has been noted to behave more like an organic solvent than like water. Therefore, an adsorbed layer of random copolymers that mimics the function of disordered proteins could, in principle, protect and enhance the proteins’ enzymatic activity even in organic solvents, which are ideal when the products and/or the reactants have limited solubility in aqueous media. Here, we demonstrate via multiscale simulations that random copolymers efficiently incorporate proteins into different solvents with the potential to optimize their enzymatic activity. We investigate the key factors that govern the ability of random copolymers to encapsulate proteins, including the adsorption energy, copolymer average composition, and solvent selectivity. The adsorbed polymer chains have remarkably similar sequences, indicating that the proteins are able to select certain sequences that best reduce their exposure to the solvent. We also find that the protein surface coverage decreases when the fluctuation in the average distance between the protein adsorption sites increases. The results herein set the stage for computational design of random copolymers for stabilizing and delivering proteins across multiple media.},
doi = {10.1073/pnas.1806207115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 26,
volume = 115,
place = {United States},
year = {2018},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1073/pnas.1806207115

Citation Metrics:
Cited by: 4 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Amphipols: Polymers that keep membrane proteins soluble in aqueous solutions
journal, December 1996

  • Tribet, C.; Audebert, R.; Popot, J. -L.
  • Proceedings of the National Academy of Sciences, Vol. 93, Issue 26
  • DOI: 10.1073/pnas.93.26.15047

Formation of microdomains in a quenched disordered heteropolymer
journal, January 1989


Statistical mechanics of random heteropolymers
journal, September 1997


Phase Diagram of Random Copolymer Melts:  A Computer Simulation Study
journal, June 2004


Isotherm Equation for Water Vapor Adsorption onto Activated Carbon
journal, November 1998


Designing Sequence-Specific Copolymer Compatibilizers Using a Molecular-Dynamics-Simulation-Based Genetic Algorithm
journal, January 2017


Scaling Aspects of Block Co-Polymer Adsorption on Curved Surfaces from Nonselective Solvents
journal, May 2008

  • Hershkovits, Eli; Tannenbaum, Allen; Tannenbaum, Rina
  • The Journal of Physical Chemistry B, Vol. 112, Issue 17
  • DOI: 10.1021/jp7097894

Enzyme function in organic solvents
journal, January 1992


Globular state of branched random heteropolymers
journal, March 1993

  • Gutin, A. M.; Grosberg, A. Y.; Shakhnovich, E. I.
  • Journal of Physics A: Mathematical and General, Vol. 26, Issue 5
  • DOI: 10.1088/0305-4470/26/5/023

Phase Transition of a Disordered Nuage Protein Generates Environmentally Responsive Membraneless Organelles
journal, March 2015


Polymer Adsorption on Curved Surfaces:  A Geometric Approach
journal, August 2007

  • Hershkovits, Eli; Tannenbaum, Allen; Tannenbaum, Rina
  • The Journal of Physical Chemistry C, Vol. 111, Issue 33
  • DOI: 10.1021/jp0725073

Aqueous Sol−Gel Process for Protein Encapsulation
journal, August 2000

  • Bhatia, Rimple B.; Brinker, C. Jeffrey; Gupta, Alok K.
  • Chemistry of Materials, Vol. 12, Issue 8
  • DOI: 10.1021/cm000260f

Recognition of complex patterned substrates by heteropolymer chains consisting of multiple monomer types
journal, May 2006

  • Kriksin, Yuri A.; Khalatur, Pavel G.; Khokhlov, Alexei R.
  • The Journal of Chemical Physics, Vol. 124, Issue 17
  • DOI: 10.1063/1.2191849

Protein misfolding and aggregation in cataract disease and prospects for prevention
journal, May 2012


Random heteropolymers preserve protein function in foreign environments
journal, March 2018


Phase transitions in random copolymers
journal, May 1993

  • Nesarikar, A.; Olvera de la Cruz, M.; Crist, B.
  • The Journal of Chemical Physics, Vol. 98, Issue 9
  • DOI: 10.1063/1.464729

Random heteropolymer adsorption on disordered multifunctional surfaces: Effect of specific intersegment interactions
journal, October 1998

  • Srebnik, Simcha; Chakraborty, Arup K.; Bratko, Dusan
  • The Journal of Chemical Physics, Vol. 109, Issue 15
  • DOI: 10.1063/1.477285

Thermodynamic procedure to synthesize heteropolymers that can renature to recognize a given target molecule.
journal, December 1994

  • Pande, V. S.; Grosberg, A. Y.; Tanaka, T.
  • Proceedings of the National Academy of Sciences, Vol. 91, Issue 26
  • DOI: 10.1073/pnas.91.26.12976

Random copolymers that protect proteins
journal, March 2018


Polymer solutions near an interface. Adsorption and depletion layers
journal, November 1981


Adsorption of random copolymers on disordered surfaces
journal, January 1998

  • Bratko, D.; Chakraborty, Arup K.; Shakhnovich, E. I.
  • Computational and Theoretical Polymer Science, Vol. 8, Issue 1-2
  • DOI: 10.1016/S1089-3156(98)00023-3

Scaling Description of a Colloidal Particle Clothed with Polymers
journal, June 1998


Phase diagram of random copolymers
journal, July 1993


Improving enzymes by using them in organic solvents
journal, January 2001


Scaling theory of polymer adsorption
journal, January 1976


Strategies for Stabilization of Enzymes in Organic Solvents
journal, November 2013

  • Stepankova, Veronika; Bidmanova, Sarka; Koudelakova, Tana
  • ACS Catalysis, Vol. 3, Issue 12, p. 2823-2836
  • DOI: 10.1021/cs400684x

Strong Selective Adsorption of Polymers
journal, May 2015


Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies
journal, January 2018

  • Louie, Raymond H. Y.; Kaczorowski, Kevin J.; Barton, John P.
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 4
  • DOI: 10.1073/pnas.1717765115

Structure of Adsorbed Polymers on a Colloid Particle
journal, June 2006

  • Yang, Shuang; Yan, Dadong; Shi, An-Chang
  • Macromolecules, Vol. 39, Issue 12
  • DOI: 10.1021/ma060014a

Random copolymers in concentrated solutions
journal, September 1996


Phase Diagram of Random Heteropolymers
journal, May 2004


Thermodynamics of random copolymer melts
journal, August 1991


Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters
journal, May 2016

  • Nott, Timothy J.; Craggs, Timothy D.; Baldwin, Andrew J.
  • Nature Chemistry, Vol. 8, Issue 6
  • DOI: 10.1038/nchem.2519

Polymer adsorption in a poor solvent
journal, February 1991


VMD: Visual molecular dynamics
journal, February 1996