Synthesis and evaluation of tetrahydropyrrolo[1,2-]quinolin-1(2)-ones as new tubulin polymerization inhibitors.

Here we explored new 1,5-disubstituted pyrrolidin-2-ones 1, 2 and 5-aryl-3,3,4,5-tetrahydropyrrolo[1,2-]quinoline-1(2)-ones 3 as inhibitors of tubulin polymerization. We evaluated their effects on microtubule dynamics and on the proliferation of A549 cells, using flow cytometry-based cell cycle analysis. The results were verified with phase-contrast microscopy in three cancer cell lines: A549, HeLa and MCF-7.

VII Congress of Russian Biophysicists-2023, Krasnodar, Russia.

This special issue of Biophysical Reviews contains the materials presented at the VII Congress of Biophysicists of Russia, held from 17 to 23 April in Krasnodar. We believe that we have managed to prepare a selection of articles that well reflects the current state of biophysical science in Russia and its place in the world science. The VII Russian Congress on Biophysics was held in Krasnodar in April 2023, continuing the tradition of the series of biophysics conferences held every 4 years.

Measuring and modeling forces generated by microtubules.

Tubulins are essential proteins, which are conserved across all eukaryotic species. They polymerize to form microtubules, cytoskeletal components of paramount importance for cellular mechanics. The microtubules combine an extraordinarily high flexural rigidity and a non-equilibrium behavior, manifested in their intermittent assembly and disassembly.

Microtubule rescue control by drugs and MAPs examined with in vitro pedestal assay.

Microtubules are essential cytoskeletal polymers, which exhibit stochastic transitions between assembly and disassembly, known as catastrophes and rescues. Understanding of catastrophes, rescues, and their control by drugs and microtubule associated proteins (MAPs) has been informed by in vitro reconstitutions of microtubule dynamics. In such experiments microtubules are typically observed on a flat surface of the coverslip.

An open call for contributions to a special issue of highlighting the research themes of VII Congress of Russian Biophysicists 2023.

We announce a call for contributions to a Special Issue of associated with the VII Congress of Russian Biophysicists (to be held in Krasnodar, Russia, 17-23 April 2023). The Congress is the main biophysical meeting held within Russia and is organized every four years. The Congress will focus on both the physical principles and mechanisms of biological processes occurring at different levels of structural organization, from molecular to cellular to organism and to population levels.

Theory of tip structure-dependent microtubule catastrophes and damage-induced microtubule rescues.

Microtubules are essential cytoskeletal polymers that exhibit stochastic switches between tubulin assembly and disassembly. Here, we examine possible mechanisms for these switches, called catastrophes and rescues. We formulate a four-state Monte Carlo model, explicitly considering two biochemical and two conformational states of tubulin, based on a recently conceived view of microtubule assembly with flared ends.

Regulation of microtubule dynamics, mechanics and function through the growing tip.

Microtubule dynamics and their control are essential for the normal function and division of all eukaryotic cells. This plethora of functions is, in large part, supported by dynamic microtubule tips, which can bind to various intracellular targets, generate mechanical forces and couple with actin microfilaments. Here, we review progress in the understanding of microtubule assembly and dynamics, focusing on new information about the structure of microtubule tips.

Expanding Stereoelectronic Limits of - Cyclizations: Synthesis of Benz[]azepines from Donor-Acceptor Cyclopropanes.

The importance of intramolecular constraints in cyclic transition-state geometries is especially pronounced in -- cyclizations, where the usual backside approach of a nucleophile to the breaking bond is impossible for the rings containing less than eight atoms. Herein, we expand the limits of - cyclizations and show that donor-acceptor cyclopropanes can provide a seven-membered ring via a genuine 6-- process. Substrates containing a -alkyl--arylcarbamoyl moiety as an acceptor group undergo Lewis acid-induced cyclization to form tetrahydrobenz[]azepin-2-ones in high yields.

Correction: Brownian dynamics simulation of protofilament relaxation during rapid freezing.

[This corrects the article DOI: 10.1371/journal.pone.

Brownian dynamics simulation of protofilament relaxation during rapid freezing.

Electron cryo-microscopy (Cryo-EM) is a powerful method for visualizing biological objects with up to near-angstrom resolution. Instead of chemical fixation, the method relies on very rapid freezing to immobilize the sample. Under these conditions, crystalline ice does not have time to form and distort structure.

Mechanisms of microtubule dynamics and force generation examined with computational modeling and electron cryotomography.

Microtubules are dynamic tubulin polymers responsible for many cellular processes, including the capture and segregation of chromosomes during mitosis. In contrast to textbook models of tubulin self-assembly, we have recently demonstrated that microtubules elongate by addition of bent guanosine triphosphate tubulin to the tips of curving protofilaments. Here we explore this mechanism of microtubule growth using Brownian dynamics modeling and electron cryotomography.

Mechanical properties of tubulin intra- and inter-dimer interfaces and their implications for microtubule dynamic instability.

Thirteen tubulin protofilaments, made of αβ-tubulin heterodimers, interact laterally to produce cytoskeletal microtubules. Microtubules exhibit the striking property of dynamic instability, manifested in their intermittent growth and shrinkage at both ends. This behavior is key to many cellular processes, such as cell division, migration, maintenance of cell shape, etc.