In this study, we have proposed and tested a new area in the drug delivery and remote control. This strategy implies the use of single domain magnetic nanoparticles (MNPs) as mediators for nanomechanical actuation of biochemical system at molecular level. The deforming force is applied to macromolecules (MM) as a result of turning MNPs under exposure to non-heating external extremely-low frequency magnetic field (ELF MF). Depending on whether the macromolecule (MM) is linked to one or two/several MNPs/anchors (which is determined by the concentration of MNPs in the suspension), two different mechanisms of action of magnetic field on MM—hydrodynamic and contact can be realized. The first is similar to the hydrodynamic stretching of a macromolecule in a liquid. The force applied to the MM in this case is proportional to ULF MF frequency f, media viscosity η, and hydrodynamics radius Rhd of MNPs. The second situation is similar to macromolecule deformation with magnetic tweezers. In this case, maximum deforming force is proportional to the square of Rhd and does not depend on ηand f. MM deformation may alter interatomic spacing, angle between the linkers, intramolecular dynamics and conformation, leading to changes in MM bioactivity.
Interaction between MNPs oscillating in ELF MF, and live cell membranes, exosomes, liposomes, etc. may result in loosening of the membrane structures, latter then become more penetrable for molecules both from inside and outside the capsule. Besides, MNPs attached to a cell membrane by functionalized linkers are able to selectively affect individual receptors and ionic channels.
Experimental results obtained do not contradict with some developed models of nanomechanical biosystem actuation at molecular level in the absence of any heating in the field.
The work was supported by grants from Ministry of Education and Science of the Russian Federation (grants 11.G34.000 and K1-2014-022), and from Russian Science Foundation (RSF grant 14-13-00731).
REFERENCES
Golovin Yu.I., Gribanovskii S.L., Golovin D.Yu., Klyachko N.L., Kabanov A.V. Single-Domain magnetic nanoparticles in an alternating magnetic field as mediators of local deformation of the surrounding macromolecules // Physics of the Solid State. 2014. V. 56. No. 7. P. 1342–1351.
Golovin Yu.I., Klyachko N.L., Golovin D.Yu., Efremova M.V., Samodurov A.A., Sokolski-Papkov M., Kabanov A.V. A New approach to the control of biochemical reactions in a magnetic nanosuspension using a low-frequency magnetic field // Technical Physics Letters.
Klyachko N.L., Sokolsky-Papkov M., Pothayee N., Efremova M.V., Gulin D.A., Pothayee N., Kuznetsov A.A., Majouga A.G., Riffle J.S., Golovin Y.I., Kabanov A.V. Changing the Enzyme Reaction Rate in Magnetic Nanosuspensions by a Non-Heating Magnetic Field // Angew. Chem. Int. Ed. 2012. V. 51. P. 1 – 5.