Controlling the diameter, monodispersity, and solubility of ApoA1 nanolipoprotein particles using telodendrimer chemistry

Wei Hi, Juntao Luo, Feliza Bourguet, Li Xing, Sun K. Yi, Tingjuan Gao, Craig Blanchette, Paul Henderson, Edward Kuhn, Mike Malfatti, William J Murphy, R. Holland Cheng, Kit Lam, Matthew A Coleman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Nanolipoprotein particles (NLPs) are nanometer-scale discoidal particles that feature a phospholipid bilayer confined within an apolipoprotein "scaffold," which are useful for solubilizing hydrophobic molecules such as drugs and membrane proteins. NLPs are synthesized either by mixing the purified apolipoprotein with phospholipids and other cofactors or by cell-free protein synthesis followed by self-assembly of the nanoparticles in the reaction mixture. Either method can be problematic regarding the production of homogeneous and monodispersed populations of NLPs, which also currently requires multiple synthesis and purification steps. Telodendrimers (TD) are branched polymers made up of a dendritic oligo-lysine core that is conjugated to linear polyethylene glycol (PEG) on one end, and the lysine "branches" are terminated with cholic acid moieties that enable the formation of nanomicelles in aqueous solution. We report herein that the addition of TD during cell-free synthesis of NLPs produces unique hybrid nanoparticles that have drastically reduced polydispersity as compared to NLPs made in the absence of TD. This finding was supported by dynamic light scattering, fluorescence correlation spectroscopy, and cryo transmission electron microscopy (Cryo-EM). These techniques demonstrate the ability of TDs to modulate both the NLP size (6-30 nm) and polydispersity. The telodendrimer NLPs (TD-NLPs) also showed 80% less aggregation as compared to NLPs alone. Furthermore, the versatility of these novel nanoparticles was shown through direct conjugation of small molecules such as fluorescent dyes directly to the TD as well as the insertion of a functional membrane protein.

Original languageEnglish (US)
Pages (from-to)1078-1086
Number of pages9
JournalProtein Science
Volume22
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

Nanoparticles
Solubility
Apolipoproteins
Polydispersity
Lysine
Phospholipids
Membrane Proteins
Cryoelectron Microscopy
Cholic Acid
Molecules
Fluorescence Spectrometry
Dynamic light scattering
Transmission Electron Microscopy
Fluorescent Dyes
Particle Size
Scaffolds
Self assembly
Purification
Polymers
Agglomeration

Keywords

  • Apolipoprotein
  • Cell-free expression
  • Membrane protein
  • Mono-dispersity
  • Nanolipoproteins
  • Nanotechnology
  • Telodendrimer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Controlling the diameter, monodispersity, and solubility of ApoA1 nanolipoprotein particles using telodendrimer chemistry. / Hi, Wei; Luo, Juntao; Bourguet, Feliza; Xing, Li; Yi, Sun K.; Gao, Tingjuan; Blanchette, Craig; Henderson, Paul; Kuhn, Edward; Malfatti, Mike; Murphy, William J; Cheng, R. Holland; Lam, Kit; Coleman, Matthew A.

In: Protein Science, Vol. 22, No. 8, 08.2013, p. 1078-1086.

Research output: Contribution to journalArticle

Hi, Wei ; Luo, Juntao ; Bourguet, Feliza ; Xing, Li ; Yi, Sun K. ; Gao, Tingjuan ; Blanchette, Craig ; Henderson, Paul ; Kuhn, Edward ; Malfatti, Mike ; Murphy, William J ; Cheng, R. Holland ; Lam, Kit ; Coleman, Matthew A. / Controlling the diameter, monodispersity, and solubility of ApoA1 nanolipoprotein particles using telodendrimer chemistry. In: Protein Science. 2013 ; Vol. 22, No. 8. pp. 1078-1086.
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AU - Yi, Sun K.

AU - Gao, Tingjuan

AU - Blanchette, Craig

AU - Henderson, Paul

AU - Kuhn, Edward

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AU - Lam, Kit

AU - Coleman, Matthew A

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