Cells can die a peaceful or violent death. The peaceful way of dying is known as apoptosis, when a series of coordinated processes lead to cell's self-destruction. Proper balance between cell proliferation and apoptosis 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 the stroke, for example. Necrotic cells spill out their components, which can produce dangerous inflammation.
One major difference between necrotic and apoptotic types of death is cell volume behavior. Necrotic cells swell and eventually rupture; apoptotic cells shrink. Cell shrinkage is one of the most essential characteristics of apoptosis and, at the same time, one of the least understood. Apoptotic shrinkage results partly from water expulsion from 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?
Cell volume regulation in apoptosis is one subject of our study. We are also studying the effects of shrinkage on cell signaling. We showed that shrinkage by itself can act as a direct apoptotic signal, and now we are trying to identify the specific components that sense cell density.
We use a technique invented in our lab, transmission-through-dye (TTD) microscopy, which permits convenient visualization of the 3D cell shape and accurate measurement of cell volume. We continue to develop other methods that open new possibilities in this research area, such as measuring cell protein content and quantification of intracellular ions.
Selected recent publications:
Rana PS, Kurokawa M, Model MA. Evidence for macromolecular crowding as a direct apoptotic stimulus. J Cell Sci, vol. 133 No. 8
Model MA, Petruccelli JC. 2018. Intracellular macromolecules in cell volume control and methods of their quantification. Curr Top Membr, 81:237-289.
Rana PS, Gibbons BA, Vereninov AA, Yurinksaya VE, Clements RJ, Model TA, Model MA. 2018. Calibration and characterization of intracellular Asante Potassium Green probes, APG-2 and APG-4. Anal Biochem 567:8-13.
Mudrak NJ, Rana PS, Model MA. 2017. Calibrated brightfield-based imaging for measuring intracellular protein concentration. Cytometry 93:297-304
Model MA. 2017. Methods for cell volume measurement. Cytometry 93A:281-296.
Model MA. 2014. Possible causes of apoptotic volume decrease: an attempt at quantitative review. Am J Physiol 306:C417-C424.
Past collaboration with Anatoly Khitrin
Anatoly Khitrin (1955-2017) was a professor in the Chemistry Department of KSU. His specialty was nuclear magnetic resonance and quantum theory, but he possessed a vast knowledge of all branches of science (https://physicstoday.scitation.org/do/10.1063/PT.6.4o.20180921a/full/). I was fortunate to work with him on several projects. On one occasion, he proposed a highly original theory of membrane potential (1); another time, he came up with an extremely simple and original description of microscopic image formation (2). We hope to develop his ideas into a working tool for analyzing brightfield transmission images.
Khitrin AK, Khitrin KA, Model MA. 2014. A model for membrane potential and intracellular ion distribution. Chem Phys Lipids. 184:76-81.
Khitrin AK, Petruccelli JC, Model MA. 2017. Bright-field microscopy of transparent objects: a geometrical optics approach. Microsc Microanal, DOI: 10.1017/S1431927617012624.
You will find links to these articles at the bottom of this screen
Ph.D, Biophysics, University of Michigan, M.S., B.S., Physics of Materials, Leningrad Polytechnic Institute