Coupling of physical characteristics of non-ionizing irradiation to specific mechanisms of cell death: are we there yet?

Abstract

The recent discovery of the various specific" triggers" and mechanisms of cell life and death responses suggests that certain non-ionizing irradiation spectra and other physical signals could be coupled with specific cellular "triggers" to improve diagnostic or treatment effects. Genetic, chemical and/or physical modifications of specific extrinsic cellular "triggers" have centered on chemical binding of specific molecules to specific receptors, i.e. chemical " triggers" thus allowing development of specific drugs to counteract the initiating function of the "triggers" in single cells. Investigations of non-ionizing irradiation effects on cells and tissues indicate that their "triggers" involve intimate interactions of linked components of the extracellular matrix and the cytoskeleton in tissues. Therefore, the search for single "triggers" that may work well for chemical "triggers" in single cells in culture may not be effective for discovery of the mechanisms that initiate sensing of the stimulations of non-ionizing irradiation and mechanical force.In cell biology, the mechanisms of life and death usually involve a series of complex, chemical, mechanical and/or electrical events that are highly interactive with many other physiological and pathological mechanisms within and outside the cell. To distinguish one event from any of the others the following things have to be established:1. Precise description of the ultimate cellular response to be studied i.e. cell death, cell movement, energy production, protein synthesis, cell division, etc. The definitions of these responses could and should be refined as an investigator finds out more information about the events in his studies. For example, cell death could be due to apoptosis (identified by production of apoptotic bodies) therefore future studies could be focused on finding markers of the extrinsic or intrinsic apoptotic pathways.2. Identification of a specific act or " triggered" reaction that initiates a series of events which produces the cellular response to be studied. For example, apoptosis can be "triggered" by ligand binding of tumor necrosis factor (TNF) to the "death receptor" found on the surfaces of certain cells.3. "Markers" are the key substance(s) or reaction(s) that distinguish a specific series of events. The series can produce several markers along the way. For instance, a key marker of apoptosis is the production of caspase 8.4. Identification of "end points", the results or cellular responses of the series of events or a subset of events. These are frequently are measureable thus useful for mathematical modeling. Ultimate cell responses such as cell death are "endpoints" but other well-defined products or reactions found within the series of events, such as caspase 8 production which occurs early in apoptosis also can be designated as desired endpoints of study. Keynote Paper Energy-based Treatment of Tissue and Assessment VIII, edited by Thomas P. Ryan Proc. of SPIE Vol. 9326, 932603 · © 2015 SPIE · CCC code: 1605-7422/15/$18