Optical microscopy for characterization of cell nanoarchitecture

Existing optical microscopy techniques offer us powerful tools to visualize cellular structure at the microscale. However, their capability of nanoscale sensitivity is restricted by the diffraction-limited resolution (~200-400 nanometers). At the same time, some of the most fundamental building blocks of the cell (cytoskeleton, intracellular membranes, ribosomes, nucleosomes, etc.) have sizes at the nanoscale. We are developing a novel spectroscopic microscopy technique capable of quantification of intracellular structure at subdiffractional length scales. The technique measures the statistical properties of intracellular spatial density variations with, in principle, an unlimited resolution. In particular, this novel technique is sensitive to the nanoscale architecture of a cell. Our data show that cellular nanoarchitecture is exceedingly well conserved among various cell types and is one of the first cell properties to undergo alteration in disease such as cancer. Indeed, the increase in the disorder in cell nanoscale architecture is one of the earliest markers of neoplasia and occurs prior to the development of any conventional markers of carcinogenesis. Our goals is to uncover the relationship between cell nanoarchitecture and molecular events in carcinogenesis, which will allow more complete understanding the initial stages of this disease.

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Backman's Biophotonics Laboratory at Northwestern University

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