209 Gen. Physiol. Biophys. (2013), 32, 209–214 doi: 10.4149/gpb_2013022 Attenuation of the insulin amyloid aggregation in presence of Fe 3 O 4 - based magnetic fluids * Katarina Siposova 1,2 , Eva Bystrenova 3 , Andrea Antosova 1 , Martina Koneracka 1 , Vlasta Zavisova 1 , Peter Kopcansky 1 and Zuzana Gazova 1 1 Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Košice, Slovak Republic 2 Department of Biochemistry, P. J. Safarik University, Moyzesova 11, 041 54 Košice, Slovak Republic 3 CNR – Instituto per lo Studio dei Materiali Nanostrutturati, via Gobetti 101, I-40129 Bologna, Italy Abstract. Presence of protein amyloid deposits is associated with pathogenesis of amyloid-related diseases. Insulin amyloid aggregates have been reported in a patient with diabetes undergoing treatment by injection of insulin. We have investigated the interference of insulin amyloid aggrega- tion with two Fe 3 O 4 -based magnetic fluids. Te magnetic fluids are able to inhibit insulin amyloid fibrillization and promote disassembly of amyloid fibrils. Te cytotoxic effect of amyloid fibrils is attenuated in presence of magnetic fluids probably due to reduction of the fibrils. We suggest that present findings propose the potential use of Fe 3 O 4 -based magnetic fluids as the therapeutic agents targeting insulin-associating amyloidosis. Key words: Amyloid aggregation — Insulin — Magnetic fluid — Cell viability Short Communication Correspodence to: Zuzana Gazova, Institute of Experimental Phys- ics, Slovak Academy of Sciences, Watsonova 47, 040 01 Košice, Slovak Republic E-mail: gazova@saske.sk * Tis article was presented at the 5 th Slovak Biophysical Sympo- sium, organised by Te Slovak Biophysical Society in Bratislava, March 19–21, 2012 Amyloid aggregates of proteins are highly ordered structures whose occurrence is associated with a number of pathologies, such as Alzheimer’s and Huntington’s diseases, spongiform encephalopathies, type-II diabetes and various systemic amyloidosis. Te amyloid deposits localized in various parts of human body are characteristic of the presence of a single predominant protein that is typical for a given disease (Sipe 2005). Up to now, there are more than 25 human proteins related to amyloid diseases. Although the amyloid-related proteins do not reveal any similarities, the amyloid aggregates (oligomers, pores, protofibrils, fibrils) share similar structural and physicochemical properties (Klunk et al. 1989; Sunde and Blake 1997). Recently, it has been found that ability to form amyloid structures is not restricted to the proteins linked to amyloid diseases, but represents the generic feature of the polypeptide chain (Bucciantini et al. 2002). It allows in vitro formation of amyloid aggregates which can be induced by high protein concentration, extreme values of pH (acid, basic), heating, interaction with various surfaces, agitation, etc. (Hamada and Dobson 2002; Dobson 2004). Insulin amyloid deposits have been found in the sites of subcutaneous insulin application in patients with diabetes long-term treated by insulin. Moreover, insulin amyloid ag- gregation causes a serious problem in the production, storage and delivery of this important biopharmaceutical compound as well as in application of the insulin pumps. In vitro insulin amyloid fibrillization can be achieved at acid pH and pres- ence of strong denaturants (guanidine hydrochloride, urea) or salts (NaCl) (Brange et al. 1997). No real cure is currently directed toward the amyloid-related diseases and still remains unclear which step in the cascade of amyloid formation is the most toxic. Te current models suggest a direct effect of amyloid structures on cell membrane stabilization (pore formation, permeation effect) (Anguiano et al. 2002) or an indirect effect of amyloid assemblies on cel- lular mechanisms (Conte et al. 2003). Te current approaches, however, suggest that reduction of the amyloid aggregation by direct inhibition of amyloid fibrillization or clearance of amyloid aggregates are beneficial (Cohen and Kelly 2003). Te growing attention concerns to the study of the effect of nanoparticles on protein amyloid aggregation due to the