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Local thermal activation of single living cells and measurement of temperature gradients in trace amounts

A practical method of creating and measuring of temperature gradients in micro and nanovolumes inside single living cells and its theoretical justification was presented by researcher at the Institute of Theoretical and Experimental Biophysics of the RAS - Vadim Tseeb, which is designed in collaboration with colleagues from DepartmentofPhysics, FacultyofScienceandEngineering, Waseda University, Tokyo, Japan. Results of these findings were recently published in leading scientific journals, including Nature Methods and Nature Scientific Reports in 2015.

These studies, which appeared at the intersection of biology, medicine, biophysics and thermodynamics of micro- and nanosystems, may fix the Russian science in the leading group of most interesting and extremely promising new direction. In a series of recent joint publications (1-5), the authors found the thermodynamic phenomena in micro- and nanovolumes of the living cells, that with no doubt will make a revolutionary overturn in the field of regenerative medicine.

The picture demonstrates the effect of ultralocal constant temperature gradient (about 2 ° C / 10 microns), induced by focused radiation IRlaser of 1455nm, to a neuron. The neuron outgrowths begin to grow in the direction of the heat source at an unprecedented rate - around 10 microns per minute. Moreover, the artificially damaged outgrowth in such a stationary temperature "field" is quickly restored in the direction, preset by the experimenters. The same effect also has been registered for HeLa-cells (irreversible protrusion on the temperature gradient), what is more the authors were able to prove (NatureScientific Reports 2015) that in both cases the growth is happening due to irreversible (directed along the temperature gradient) formation of intracellular cytoskeletal structures. The ability to manage the dynamics and directionality of cell growth, by pulling them in the right direction with such incredible speed, offers unprecedented practical prospects for the application of this method for rapid recovery of individual cells and tissues in medicine and biotechnology by a guidance of ultralocal stationary temperature gradients (Tgradient-3D printing)

In another series of studies, the authors used nanoheater - metal nanoparticle, fused at the tip of a glass micropipette, heated by IRlaser of 1064 nm. In such a configuration the incredible stationary temperature gradients were obtained in the aqueous medium near the living cell (up to 70 ° C / 20 microns), that makes it easy to boil (destroy) a single living cell, whereas a neighboring cell will experience a temperature increase of only a few degrees Features of such a micromanipulations in living tissues can hardly be overestimated. In addition, the huge speeds of stabilization of temperature gradients in microvolumes (millisecond range) were achieved with experimental configuration with nanoheater, that allowed to obtain a new instrumental approach for ultra-fast, non-invasive manipulations by local intracellular parameters - such as, for example, the intracellular concentration of calcium ions (HFSP 2009), where a most interesting effect of release of calcium ions from intracellular compartments at the millisecond phase of cell cooling was obtained.

A course of problems exposed by the authors, has caused a lively discussion of many research groups, published in (Nature Methods, 2015). The most important thing in this discussion is that the thermodynamic intracellular phenomena in micro- and nanovoluimes of a cell were clearly undervalued. Heat transfer phenomenas in a living cell, as well as in micro and nanostructures of semiconductors and microprocessors (that became known to engineers in the last 20 years), are not subject to the Fourier thermal conductivity equation, but determined for the most part by the Kapitza contact thermal resistance, that entails an abnormally large gradients of temperature in the micro- and nanostructures. Therefore, endogenous sources of heat (even open ion channels) have the potential to instantly warm nanovolumes of a living cells up to tens of degrees!

These experimental approaches offer new fundamental and applied horizons in the study and management of the dynamics of intracellular physiological processes and extracellular responses on single living cells, that already has made it possible to detect thermally-induced gene expression processes in a single (selected) cell, initiation of muscle contraction of single myocyte, directed protrusion of cytoskeletal structure of a cell by microscopic temperature gradient, the release of intracellular calcium in the phase of ultra-rapid cooling of a single cell, induction of transmembrane electric currents and certainly the most impressive - the detection of directional growth of neuronal outgrowths and their regeneration (after the dotted mechanical destruction) in the presence of a microscopic temperature gradient. The latter is really seems like fantastic, if it was not already a published reality. It is now possible to introduce an algorithm of creating of invitro functional, artificially constructed neural circuits with desired properties for the study of the fundamental principles of storage and transmission of information by nerve cells and for the cultivation of such structures invivo. In the case of neurosurgical medical indications where it is extremely necessary to create neural interfaces to control bionic prostheses, this method is certainly ready for practical application.

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