Controlling the Self-Assembly of Biomolecules into Functional Nanomaterials through Internal Interactions and External Stimulations: A Review

Abstract

Biomolecular self-assembly provides a facile way to synthesize functional nanomaterials. Due to the unique structure and functions of biomolecules, the created biological nanomaterials via biomolecular self-assembly have a wide range of applications, from materials science to biomedical engineering, tissue engineering, nanotechnology, and analytical science. In this review, we present recent advances in the synthesis of biological nanomaterials by controlling the biomolecular self-assembly from adjusting internal interactions and external stimulations. The self-assembly mechanisms of biomolecules (DNA, protein, peptide, virus, enzyme, metabolites, lipid, cholesterol, and others) related to various internal interactions, including hydrogen bonds, electrostatic interactions, hydrophobic interactions, π⁻π stacking, DNA base pairing, and ligand⁻receptor binding, are discussed by analyzing some recent studies. In addition, some strategies for promoting biomolecular self-assembly via external stimulations, such as adjusting the solution conditions (pH, temperature, ionic strength), adding organics, nanoparticles, or enzymes, and applying external light stimulation to the self-assembly systems, are demonstrated. We hope that this overview will be helpful for readers to understand the self-assembly mechanisms and strategies of biomolecules and to design and develop new biological nanostructures or nanomaterials for desired applications.

Keywords: biomolecules; external stimulations; interactions; nanostructures; self-assembly.

Figure 1

Hydrogen bonds promoted the self-assembly of biomolecules: (a) Hydrogen-bond-induced self-assembly of FF into nanofibers, microtubes, and microrods. Reprinted with permission from [21]. Copyright 2015 American Chemical Society. (b) The formation of microscale peptide nanowires (PNWs)–graphene array. Reprinted with permission from [52]. Copyright 2013 American Chemical Society.

Figure 2

Electrostatic-interaction-mediated self-assembly of biomolecule-based nanomaterials: (a) The formation of peptide nanofiber (PNF)-bioinspired silver nanowires (AgNWs) on graphene nanosheets (GNs). Reprinted with permission from [58]. Copyright 2014 American Chemical Society. (b) The synthesis of self-assembled P22 virus-like particles (VLPs) via rigid (inorganic nanoparticles (NPs)) and soft (PAMAM) cationic linkers. Reprinted with permission from [59]. Copyright 2017 Materials Research Society. (c) The structure-based design of protein nanowires. Reprinted with permission from [60]. Copyright 2016 American Chemical Society. (d) Protein nanosheet–quantum dot (QD) nanohybrids. Reprinted with permission from [61]. Copyright 2017 American Chemical Society. PEI, polyethyleneimine; FRET, fluorescence resonance energy transfer.

Figure 3

The hydrophobic interaction for biomolecular self-assembly: (a) A pyrene-labeled peptide for monitoring the protein–peptide interactions. Reprinted with permission from [71]. Copyright 2011 American Chemical Society. (b) Self-assembly of bovine serum albumin (BSA)-based nanoparticles to microspheres. Reprinted with permission from [72]. Copyright 2017 American Chemical Society. GO, graphene oxide.

Figure 4

π–π-interaction-mediated self-assembly of nanomaterials: (a) The fabrication of PNF– graphene quantum dot (GQD) nanohybrids. Reprinted with permission from [76]. Copyright 2015 WILEY-VCH. (b) The synthesis of GO–PNF nanohybrids and GO-PNF-HA minerals. Reprinted with permission from [33]. Copyright 2015 Elsevier. (c) The synthesis of PNFs and binary GQD-PNF, and ternary GQD–PNF–GO nanohybrids. Reprinted with permission from [77]. Copyright 2017 WILEY-VCH.

Figure 5

The in vitro genetic-encoding-mediated self-assembly of DNA to different nanostructures: (a,b) nanowires and (c,d) two-dimensional (2D) nanosheets. Reprinted with permission from [85]. Copyright 2016 Macmillan Publishers Limited. 1D, one dimensional.

Figure 6

The avidin–biotin-binding-mediated self-assembly of a protein cage to three-dimensional (3D) functional crystals. Reprinted with permission from [95]. Copyright 2014 Macmillan Publishers Limited.

Figure 7

The pH effect on the self-assembly of biomolecules: (a) Self-assembled fibers and tubes under different pH conditions. Reprinted with permission from [112]. Copyright 2017 American Chemical Society. (b) The pH-triggered morphological transition of self-assembling PA. Reprinted with permission from [113]. Copyright 2012 American Chemical Society. (c) Self-assembled nanofibers by pH-mediated lateral assembly. Reprinted with permission from [114]. Copyright 2015 American Chemical Society.

Figure 8

The temperature effect on biomolecular self-assembly: (a) The thermo-reversible transition and (bottom right) structure of PA. Reprinted with permission from [125]. Copyright 2013 The Royal Society of Chemistry. (b) The synthesis and proposed model of self-assembly and disassembly of pH- and temperature-responsive Amelogenin (AME)–PNIPAm bioconjugates. Reprinted with permission from [126]. Copyright 2018 WILEY-VCH.

Figure 9

Self-assembled DNA nanostructures on a mica surface by adjusting the Ni²⁺ ion concentration: (a) 3, (b) 4, and (c) 6 mM. Reprinted with permission from [132]. Copyright 2017 Wiley-VCH.

Figure 10

Effects of organic solvents on biomolecular self-assembly: (a) The structural transition of FF nanofibers in mixed organic solvents. Reprinted with permission from [136]. Copyright 2010 WILEY-VCH. (b) Vertically well-aligned peptide nanowires prepared by high-temperature aniline vapor aging. Reprinted with permission from [140]. Copyright 2008 WILEY-VCH. (c) A phase transition induced by trace amounts of organic solvent. Reprinted with permission from [142]. Copyright 2016 American Chemical Society. (d) Kinetic mechanisms of peptide self-assembly studied by molecular dynamics simulation (MDS). Reprinted with permission from [143]. Copyright 2015 American Chemical Society.

Figure 11

The enzyme-mediated self-assembly of biomolecules: (a) The enzyme-active self-assembly of water-soluble diblock copolymers to colloidal nanostructures. Reprinted with permission from [147]. Copyright 2009 American Chemical Society. (b) Alkaline phosphatase (ALP)-mediated formation of a peptide hydrogel. Reprinted with permission from [152]. Copyright 2016 The Royal Society of Chemistry. (c) The enzyme-induced self-assembly of pTP-Me into PNFs. Reprinted with permission from [155]. Copyright 2018 American Chemical Society. (d) The self-assembly of a glycopeptide to a supramolecular hydrogel. Reprinted with permission from [156]. Copyright 2018 American Chemical Society.

Figure 12

Two-dimensional peptide nanosheets (PNSs) by molecular tailoring: a schematic presentation of 2D peptide self-assembly and the biomimetic fabrication of 3D graphene foam (GF)-PNS-HA minerals. Reprinted with permission from [164]. Copyright 2018 WILEY-VCH.