Biology subjects

Frolov, N.

Publications and source records attributed to Frolov, N..

3 recordsLinked to original sources

bioRxiv2025

Beyond Arrhenius: Nonlinear and negative temperature scaling of biological rates from multi-step mechanisms

Temperature shapes all biological processes, particularly during the early development of ectothermic organisms. A widely used framework for describing temperature dependence is the Arrhenius equation, which predicts an exponential increase in rates with temperature. However, biological rates often deviate from this prediction when measured across broader temperature ranges. While negative apparent activation energies are often attributed to protein denaturation, this cannot explain similar behavior observed at temperatures where enzymes remain stable. These broader scaling patterns remain mechanistically unexplained. Here we present a general Markov chain framework for modeling biological timing as cascades of reversible, temperature-dependent steps. Applying this model to 121 published datasets spanning diverse species, biological timescales, and temperature ranges, we find that a consistent three-zone scaling pattern emerges: Arrhenius-like behavior at low and high temperatures, and a quadratic exponential regime at intermediate temperatures. We show that this pattern arises naturally from differences in activation energies across steps in the network. The quadratic exponential regime is an emergent feature of averaging across many steps and is robust to variation across network realizations. In contrast, Arrhenius-like scaling at the extremes tends to be more variable and originates from smaller sub-networks. Apparent negative activation energies can emerge naturally from the dynamics of multi-step networks, even in the absence of protein denaturation. Our framework provides a unified mechanistic explanation for diverse temperature-scaling behaviors in biology and may help predict how developmental and physiological processes respond to environmental change. Although we focus on development, the model is broadly applicable to biological systems governed by multi-step reaction networks.

systems biology↗

bioRxiv2024

The nuclear-cytoplasmic ratio controls the cell cycle period in compartmentalized frog egg extract

Each proliferating cell replicates its DNA and internal components before distributing this material evenly to its daughters. Although the regulation of cyclin-dependent kinases (Cdks) that dictate orderly cell cycle progression is well characterized, how the subcellular localization of the cell cycle machinery contributes to timing is not well understood. We investigated the influence of the nucleus by reconstituting cell cycle oscillations in droplets of frog egg extract in the absence or presence of a nuclear compartment and monitoring dynamics by time-lapse microscopy. We found that the cell cycle time increased in the presence of nuclei, which grew larger with each cell cycle. The correlation between increasing nuclear volume and a longer cell cycle period was maintained across extracts and nuclei from various Xenopus species and persisted upon inhibition of DNA replication or transcription. However, inhibition of nuclear import or the kinase Wee1 impacted the relationship between the nuclear-cytoplasmic ratio and the cell cycle period. To conceptually capture these experimental observations, we developed a computational model that incorporates cell cycle oscillations, nuclear-cytoplasmic compartmentalization, and periodic nuclear envelope breakdown and reformation. Altogether, our results support the major role of the nuclear compartment in setting the pace of the cell cycle and provide an explanation for the increase in cell cycle length observed at the midblastula transition when cells become smaller and the nuclear-cytoplasmic ratio increases.

biophysics↗

bioRxiv2020

High-level stimulus template modulates neuronal response at the earlier processing stages

There is ample evidence that the brain matches sensory information with internal templates, but the details of this mechanism remain unknown. Here we consider the processing of repeatedly presented ambiguous stimuli with high ambiguity (HA) and low ambiguity (LA) and analyze how the processing depends on the ambiguity of the previous stimulus. On the behavioral level, we report a faster response to the HA stimulus after HA stimuli and a faster response to the LA stimulus after LA stimuli. The EEG analysis reveals that when HA stimulus follows LA stimuli, the neuronal activity in the sensory areas attenuates at the early processing stage but enhances during the latter stages. It evidences the hierarchical processing organization where low levels process the stimulus details, and high levels represent its interpretation. It also confirms that on low levels, HA and LA stimuli processing is similar due to their similar morphology. Therefore, the brain uses the LA stimulus template on the low levels to reduce the demands when processing the HA stimulus details. When LA stimulus follows HA stimuli, the attenuated response in the sensory regions accompanies high response in the frontal cortex. Namely, we observe high{theta} power in the medial frontal cortex and high {beta} power in the right inferior frontal cortex. It shows activation of the top-down cognitive control functions detecting the mismatch between the LA stimulus and the HA stimulus template and transfer this template to the low processing levels. Significance statementThe brain attenuates its response to repeatedly presented similar stimuli. When an ambiguous visual stimulus follows unambiguous stimuli with the same morphology, the neuronal response in sensory areas decreases at the early processing stage but enhances during the latter stages. It evidences hierarchical processing organization where low levels process the details, and high levels represent the interpretation. It also confirms that the brain uses templates on different levels to reduce the processing demands. When an unambiguous stimulus follows ambiguous stimuli, a low response in the sensory regions accompanies high response in the frontal cortex. It manifests activation of the top-down mechanisms to detect the mismatch between an unambiguous stimulus and an ambiguous template and transfer this template to low levels.

neuroscience↗