Protein misfolding by UV emission from nanoparticles

PITTSBURGH - Aug. 2, 2016 - PRLog -- .
Introduction
Amyloid diseases like Alzheimer's and Parkinson's are not caused by bacteria or viruses, but rather by the accumulation of fibrils from misfolded proteins. NPs having enormous S/V ratios are thought [1] to somehow enhance the rate of protein fibrils by decreasing the lag time for nucleation and growth by attaching to their surfaces. NPs stand for nanoparticles and S/V for surface-to-volume. Mature fibrils are rope-like, 5-10 nm diameter up to a few microns in length. Pre-fibrillar oligomers forming on the surface of NPs are shown in the thumbnail.

Although the DNA contains all the information for life, the replication proteins actually perform the constant repair necessary for life to be to be perpetuated. However, replication proteins themselves are subject to damage by irreversible PC modification. PC stands for protein carbonylation. Since the proteins control mutation rates in DNA replication, PC damage should determine the frequency of DNA mutations, and therefore the argument [2] was made that PC damage should cause errors in DNA replication. At various PC levels, constant levels of oxidative DNA damage from ROS were controlled with UVC light. Indeed, doubling the PC damage for Escherichia coli was found correlated with over a 100-fold increase in DNA mutation rate. ROS stands for reactive oxygen species and UVC for UV radiation at 254 nm.

Problem
Currently, NPs are thought to induce protein misfolding by ROS induced PC. However, a NP mechanism to provide energies of at least 5 eV necessary to create the ROS is required, but not known.

Proposal
Protein misfolding induced by NPs is proposed to be the UV radiation created as the NPs absorb heat in vivo from the surroundings. In the thumbnail, the NPs upon absorbing heat are depicted emitting low-level UV radiation that induces misfolding by photolytic fibril nucleation and growth. ROS are not required for fibrillation.

Theory
Classical physics does not predict NPs emit UV radiation as conservation of heat proceeds by an increase in temperature. However, heat transfer in NPs is governed by the Planck law of QM that precludes conservation of heat by an increase in temperature as the heat capacity of the atoms in NPs vanishes. QM stands for quantum mechanics.

Discussion
Unlike classical physics that allows the atom to have constant heat capacity from the macro to the nanoscale, QM by the Planck law restricts heat capacity to the macroscale. At the nanoscale, the atom heat capacity depends on the EM confinement. Since NPs have high S/V ratios, heat is momentarily confined to the NP surface, and since the NPs are nanoscale, the NP atoms are spontaneously placed under EM confinement at nanoscale wavelengths. Hence, NPs by the Planck law have vanishing heat capacity. Heat therefore cannot be conserved by an increase in temperature, and therefore QED conserves the heat by creating EM radiation standing across the NP diameter. For NP diameter d and refractive index n, EM radiation is produced having half-wavelength λ / 2 = nd. For example, silver NPs having n = 1.32 and d < 95 nm emit EM radiation < 254 nm which is beyond the UVC, a lethal level for PC and DNA damage in all living systems as the pyrimidine dimers are formed that block replication. Smaller NPs emit even higher frequency EM radiation. QED stands for quantum electrodynamics, but is a far simpler theory than the QED advanced by Feynman and others. In general, see diverse QED applications at http://www.nanoqed.org/, 2010 – 2016.

Conclusions
Protein misfolding is enhanced by the UV radiation emitted from NPs upon absorbing heat from the surroundings. The UV is most intense at the NP surface thereby explaining why fibril nucleation and growth are observed at the NP surface. Amyloid diseases should therefore not be treated with NPs.

UV radiation has the Planck energy to create ROS, but ROS are not necessary for protein misfolding as fibrils nucleate and grow from the UV radiation from NPs.

High S/V ratios of NPs are important as absorbed heat is almost totally absorbed in the NP surface, thereby providing the momentary EM confinement necessary to preclude the NP atoms from having the heat capacity to increase in temperature. Therefore, conservation of heat in NPs proceeds by the creation of UV radiation standing across the NP diameter. Once the NP surface heat is expended in forming the standing EM radiation, there is no longer any EM confinement and the EM radiation escapes to the surroundings.

References
[1] S. Linse, et al., "Nucleation of protein fibrillation by nanoparticles," Proc. Nat. Acad. Scie. USA, 104, 8691-8696, 2007.
[2] A. Krisko and M. Radman, "Phenotypic and Genetic Consequences of Protein Damage," PLoS Genetics, 9, 1003810, 2013.