Michael A. Model
- Ph.D, Biophysics, University of Michigan
- M.S., B.S., Physics of Materials, Leningrad Polytechnic Institute
- Biological Light Microscopy
- Cell death
Cell volume and death
Cells can die a peaceful or a violent death. The peaceful way of dying is known as apoptosis, where a series of coordinated processes lead to cell's self-destruction. Proper balance between cell proliferation and death is necessary for normal functioning of the organism: too little apoptosis may lead to cancer,
autoimmune and inflammatory diseases, and excessive apoptosis is associated with neurodegeneration, tissue damage and AIDS.
Necrosis is the other common type of death that typically results from a more severe injury. It is often observed in stroke, for example. Necrotic cells spill out their components, which can produce dangerous inflammation.
One major difference between necrotic and apoptotic cells is their size. Necrotic cells swell and eventually rupture; apoptotic cells shrink. Indeed, the volume change is one of the most essential characteristic of apoptosis and at the same time, one of the least understood. Cell volume is determined mostly by
the amount of water contained in the cell, which takes us to the next question: what determines the amount of intracellular water? And what exactly happens during apoptosis that makes cells lose water? Furthermore, cells are definitely capable of sensing their own volume, and volume changes somehow feed back into the signaling chain. This feedback is important, and sometimes blocking cell shrinkage will prevent further progression of apoptosis.
These are the kind of questions we are studying. We use a new technique developed at KSU, transmission-through-dye (TTD) microscopy, which conveniently permits visualization and measurements of cell volume and water content and opens many new possibilities in this research area. Currently we are exploring the roles of several new potential mechanisms in the volume regulation of apoptotic cells.
The left panel is a TTD image of HeLa cells at various stages of apoptosis development, and the right panel is a corresponding fluorescence image showing caspase activation (green), the loss of mitochondrial potential (red) and condensation of chromatin (blue).
Model MA. Possible causes of apoptotic shrinkage: An attempt at quantitative review. Am. J. Physiology DOI: 10.1152/ajpcell.00328.
Model MA, Schonbrun E. Optical determination of intracellular water in apoptotic cells. J Physiol. DOI: 10.1113/jphysiol.2013.263251
Orlov SN, Model MA, Grygorczyk R. The triggering and progression of the cell death machinery can occur independently of cell volume perturbations. J. Physiology, DOI: 10.1113/jphysiol.2013.258624
Kasim NR, Kuželová K, Holoubek A, Model MA. Live fluorescence and transmission-through-dye microscopic study ofactinomycin-induced apoptosis and apoptotic volume decrease. Apoptosis 18, 521-532.
Yurinskaya VE, Moshkov AV., Wibberley AV, Lang F, Model MA, Vereninov AA. Dual response of human leukemiaU937 cells to hypertonic shrinkage: initial regulatory volume increase (RVI) anddelayed apoptotic volume decrease (AVD). Cell.Physiol.Biochem. 30:964-973. (2012)
Model MA. Imaging cell's third dimension. Microsc Today 20, 28-32 (2012)
Lababidi SL, Pelts M, Moitra M, Leff LG, Model MA. Measurement of bacterial volume by transmission-through-dye imaging. J Microbiol Methods, 87, 375-377 (2011)
Pelts M, Pandya SM, Oh CJ, Model MA. Thickness profiling of formaldehyde-fixed cells by transmission-through-dye microscopy. BioTechniques, 50, 389-396 (2011)
Model MA, Fang J, Yuvaraj P, Chen, Y, Zhang Newby B. 3D deconvolution of spherically aberrated images using commercial software. J. Microsc. 241, 94-100 (2011).
Gregg JL, McGuire KM, Focht DC, Model MA. Measurement of the thickness and volume of adherent cells using transmission-through-dye microscopy. Pflugers Arch. 460, 1097-1104 (2010).
Model MA, Reese JL, Fraizer GC. Measurement of wheat germ agglutinin binding with a fluorescence microscope. Cytometry 75A, 874-881 (2009).
Model MA, Khitrin AK, Blank JL. Measurement of the absorption of concentrated dyes and their use for quantitative imaging of surface topography. J. Microsc. 231, 156-167 (2008).
Model MA, Blank JL. Concentrated dyes as a source of two-dimensional fluorescent field for characterization of a confocal microscope. J. Microsc. 229, 12-16 (2008).
Scholarly, Creative & Professional Activities
- Techniques in optical microscopy
- Apoptosis, necrosis
- Cell volume regulation