Search bioRxiv⌕ Search

bioRxiv · 10.1101/675223

Effect of Alpha-Lactalbumin and Lactoferrin Oleic Acid Complexes on Chromatin Structural Organization

Abstract

This work focuses on the study of multimeric alpha-lactalbumin oleic acid and lactoferrin oleic acid complexes. The purpose of the research is to study possible mechanisms involved in their pro-apoptotic activities, as seen in some tumor cell cultures. Complexes featuring oleic acid (OA) with human alpha-lactalbumin (hAl) or with bovine alpha-lactalbumin (bAl), and human lactoferrin (hLf) were investigated using small-angle neutron scattering (SANS). It was shown that while alpha-lactalbumin protein complexes were formed on the surface of polydisperse OA micelles, the lactoferrin complexes comprised a monodisperse system of nanoscale particles. Both hAl and hLf complexes appeared to interact with the chromatin of isolated nuclei affecting chromatin structural organization. The possible roles of these processes in the specific anti-tumor activity of these complexes are discussed.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lebedev, D., Zabrodskaya, Y., Pipich, V., Kuklin, A., Ramsay, E., Sokolov, A., Elizarova, A., Shaldzhyan, A., Grudinina, N., Pantina, R., Wu, B., Shtam, T., Volnitskiy, A., Shmidt, A., Shvetsov, A., Isaev-Ivanov, V., Egorov, V.. 2019-06-20. Effect of Alpha-Lactalbumin and Lactoferrin Oleic Acid Complexes on Chromatin Structural Organization. https://doi.org/10.1101/675223

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Amyloid stability and condensate material properties independently govern the hnRNPA2 condensate to fibril transition

hnRNPA2 is a component of cellular membraneless organelles many of which contain RNA and RNA-binding proteins (RBPs). RBPs frequently contain low-complexity domains (LCDs) that can also assemble into amyloid fibrils. Fibrils isolated from patients with frontotemporal lobar degeneration contain ordered segments of these LCDs and disease-associated mutations can enhance the homotypic interactions that promote aggregation. Although previous studies have largely examined the condensate-to-fibril transition by altering condensate stability, how amyloid structure governs this process remains poorly understood. Here, we show that the hnRNPA2 LCD forms a reproducible fibril fold and by combining structure-guided thermodynamic profiling, peptide design, mutagenesis and in vitro characterization under conditions with (two-phase) and without (one-phase) condensates, we define the molecular determinants of its assembly. We identify an aromatic triad within the fibril core that controls fibril formation kinetics and thermodynamic stability. Mutational analysis further reveals that condensate stability and fibril stability are largely independent. Finally, microrheology linked reduced condensate viscosity to faster fibril formation, supporting a role for condensate material properties in regulating aggregation kinetics. Together, these findings support a model in which the condensate-to-fibril transition is governed by the interplay between a disordered ''fuzzy coat'' and a fibril-forming aromatic triad within hnRNPA2. This work provides a structural framework for understanding how condensates can transition into amyloid assemblies.

biophysics↗

hAM-pe soluble extract increases human keratinocyte HaCaT cell-line mobility in scratch assays

We have studied the impact of human amniotic membrane (hAM-pe) on wound closing speed in a scratch assay of human keratinocytes (HaCaT). Though not without limitations, scratch assays are useful for studying collective cellular displacement as a model of wound healing. We show that the treatment is effective in decreasing the average time that the cells need to completely close the wound, in agreement with previous \emph{in vivo} experiments. We developed an automated segmentation software, and verified that a linear fit, though not completely describing the wound edge dynamics, is a robust method for comparing treatments and control measurements. By tracking the individual motion of a subset of cells, we found that individual treatment does not cause an increase in individual speed enough to explain the effect of the treatment at the collective (wound edge) level. Instead, the mean squared displacement and numerical simulations of a simple model of interacting active Brownian particles support the view that the main effect of the treatment at the individual level is to increase the persistence of cellular motion.

biophysics↗

Temperature-dependent Fano resonance in Microtubules and Tubulin investigated with Spontaneous Raman Spectroscopy

Microtubules are self-assembled biological hollow nanotubes composed by protein tubulin. They are essential for many biological functions, including cell motility, cell division, and act as intracellular track for organelle transport. In turn, through dynamic assembly and disassembly, they form spindle fibers for chromosome segregation during mitosis and meiosis. In this paper, we have measured the Raman spectra of microtubules and their constituent protein tubulin in dry powder form for a range of temperatures, from nitrogen liquid T=77 K up to room and physiological temperature T=310 K, to determine if molecular bond vibrations present potential Fano resonance asymmetry. We have found nontrivial persistence of Fano resonances, q<5, at room and physiological temperatures for some specific vibrational modes.

biophysics↗