Mass spectrometry imaging (MSI) provides the ability to detect and identify a broad range of analytes and their spatial distributions from a variety of sample types, including tissue sections. Here we describe an approach for probing neuropeptides from sparse cell cultures using matrixassisted laser desorption/ionization time-of-flight (MALDI-TOF) MSI-at single cell spatial resolution-in both MS and tandem MS modes. Cultures of Aplysia californica neurons are grown on an array of glass beads embedded in a stretchable layer of Parafilm M. As the membrane is stretched, the beads/neurons are separated physically and the separated beads/ neurons analyzed via MALDI TOF MS. Compared with direct MS imaging of samples, the stretching procedure enhances analyte extraction and incorporation into the MALDI matrix, with negligible analyte spread between separated beads. MALDI tandem MSI using the stretched imaging approach yields localization maps of both parent and fragment ions from Aplysia pedal peptide, thereby confirming peptide identification. This methodology represents a flexible platform for MSI investigation of a variety of cell cultures, including functioning neuronal networks.

Original languageEnglish (US)
Pages (from-to)828-836
Number of pages9
JournalJournal of the American Society for Mass Spectrometry
Issue number5
StatePublished - May 2011


  • Aplysia
  • Cell cultures
  • MSI

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy


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