Live-cell protein labelling with nanometre precision by cell squeezing

Nat Commun. 2016 Jan 29:7:10372. doi: 10.1038/ncomms10372.


Live-cell labelling techniques to visualize proteins with minimal disturbance are important; however, the currently available methods are limited in their labelling efficiency, specificity and cell permeability. We describe high-throughput protein labelling facilitated by minimalistic probes delivered to mammalian cells by microfluidic cell squeezing. High-affinity and target-specific tracing of proteins in various subcellular compartments is demonstrated, culminating in photoinduced labelling within live cells. Both the fine-tuned delivery of subnanomolar concentrations and the minimal size of the probe allow for live-cell super-resolution imaging with very low background and nanometre precision. This method is fast in probe delivery (∼ 1,000,000 cells per second), versatile across cell types and can be readily transferred to a multitude of proteins. Moreover, the technique succeeds in combination with well-established methods to gain multiplexed labelling and has demonstrated potential to precisely trace target proteins, in live mammalian cells, by super-resolution microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Cell Line
  • Cells / chemistry*
  • Cells / metabolism
  • Fluorescent Dyes / chemistry
  • Humans
  • Proteins / chemistry*
  • Staining and Labeling / methods*


  • Fluorescent Dyes
  • Proteins