Microfluidic deposition for resolving single-molecule protein architecture and heterogeneity

Nat Commun. 2018 Sep 24;9(1):3890. doi: 10.1038/s41467-018-06345-4.

Abstract

Scanning probe microscopy provides a unique window into the morphology, mechanics, and structure of proteins and their complexes on the nanoscale. Such measurements require, however, deposition of samples onto substrates. This process can affect conformations and assembly states of the molecular species under investigation and can bias the molecular populations observed in heterogeneous samples through differential adsorption. Here, we show that these limitations can be overcome with a single-step microfluidic spray deposition platform. This method transfers biological solutions to substrates as microdroplets with subpicoliter volume, drying in milliseconds, a timescale that is shorter than typical diffusion times of proteins on liquid-solid interfaces, thus avoiding surface mass transport and change to the assembly state. Finally, the single-step deposition ensures the attachment of the full molecular content of the sample to the substrate, allowing quantitative measurements of different molecular populations within heterogeneous systems, including protein aggregates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemistry
  • Analytic Sample Preparation Methods / instrumentation
  • Analytic Sample Preparation Methods / methods*
  • Feasibility Studies
  • Microfluidics / instrumentation
  • Microfluidics / methods*
  • Microscopy, Atomic Force
  • Peptide Fragments / chemistry
  • Protein Aggregates
  • Single Molecule Imaging / instrumentation
  • Single Molecule Imaging / methods*
  • alpha-Synuclein / chemistry

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Protein Aggregates
  • SNCA protein, human
  • alpha-Synuclein
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)