arXiv subjects

Adriana M. De Mendoza

Publications and source records attributed to Adriana M. De Mendoza.

5 recordsLinked to original sources

arXiv2025

Thermal Radiosensitization Beyond Misrepair: A Mechanistic Model of Temperature-Enhanced DNA Vulnerability

Objective: Hyperthermia (HT), characterized by elevated tissue temperatures above physiological levels, is a well-established radiosensitizer. When combined with radiotherapy (RT), forming thermoradiotherapy (TRT), a synergistic effect is observed across in vitro, in vivo, and clinical studies. The greatest radiosensitization occurs when HT and RT are applied simultaneously. This work aims to explore physical mechanisms -- beyond DNA repair inhibition -- that contribute to this synergy. Approach: We developed a biophysical model for the thermal enhancement ratio (TER), incorporating temperature-dependent variations in the number of vulnerable DNA sites, the DNA-ion/particle interaction cross-section, and other physicochemical parameters. These include ion production rate, diffusion processes, and medium density. The model includes misrepair effects phenomenologically, which make it consistent with other studies. Main results: The model reproduces TER values observed under simultaneous HT and RT in isolated plasmids with variable temperature. Our results indicate that, in addition to misrepair, other physical factors contribute to radiosensitization under concurrent treatment. Among these, the temperature-dependent amplification of DNA-ion/particle interaction cross-section -- driven by enhanced DNA thermal fluctuations structure -- emerges as the second most influential factor. Significance: These findings suggest that thermal radiosensitization arises not only from impaired repair, but also from increased physical vulnerability of the DNA. The model provides mechanistic insight for optimizing TRT parameters.

physics.bio-ph↗

arXiv2025

Generalized, sublethal damage-based mathematical approach for improved modeling of clonogenic survival curve flattening upon hyperthermia, radiotherapy, and beyond

Mathematical modeling can offer valuable insights into the behavior of biological systems upon treatment. Different mathematical models have been designed to predict the efficacy of hyperthermia (HT), radiotherapy (RT), or their combination. However, approaches capable of modeling cell survival from shared general principles for both mono-treatments and their co-application are rare. Moreover, some cell cultures show dose-dependent saturation in response to HT or RT, manifesting in survival curve flattening. An advanced survival model must, therefore, appropriately reflect such behavior. We propose a mathematical approach to model the effect of both treatments based on the general principle of sublethal damage (SLD) accumulation for the induction of cell death and irreversible proliferation arrest. Our approach extends Jung's model on heat-induced cellular inactivation by incorporating dose-dependent recovery rates that delineate changes in SLD restoration. The resulting unified model (Umodel) accurately describes HT and RT survival outcomes, applies to simultaneous thermoradiotherapy modeling, and is particularly suited to reproduce survival curve flattening phenomena. We demonstrate the Umodel's robust performance (R2>0.95) based on numerous clonogenic survival datasets from the literature and experiments. The proposed Umodel allows the use of a single mathematical function based on generalized SLD accumulation principles with implemented radiosensitization, regardless of energy type or mechanism of action. It reproduces various clonogenic survival curve patterns, including flattening, thus encompassing treatment variability and potentially better reflecting tumor responses. Our approach opens options for further model development and therapy outcome predictions of sequential treatments in different orders and recovery intervals.

physics.bio-ph↗

arXiv2020

Mathematical model for the thermal enhancement of radiation response: Thermodynamic approach

Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Hyperthermia (HT) is a promising option to improve the outcome of radiation treatment (RT) and is increasingly applied in hospital. However, the synergistic effect of simultaneous thermoradiotherapy is not well understood yet, while its mathematical modelling is essential for treatment planning. To better understand this synergy, we propose a theoretical model in which the thermal enhancement ratio (TER) is explained by the fraction of cells being radiosensitised by the infliction of sublethal damage through mild HT. Further damage finally kills the cell or inhibits its proliferation in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our predictions well reproduce experimental data from in-vitro and in-vivo studies, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

physics.bio-ph↗

arXiv2020

Temporal correlations of sunlight may assist photoprotection in bacterial Photosynthesis

Photosynthetic systems utilize adaptability to respond efficiently to fluctuations in their light environment. As a result, large photosynthetic yields can be achieved in conditions of low light intensity, while photoprotection mechanisms are activated in conditions of elevated light intensity. In sharp contrast with these observations, current theoretical models predict bacterial cell death for physiologically high light intensities. To resolve this discrepancy, we consider a unified framework to describe three stages of photosynthesis in natural conditions, namely light absorption, exciton transfer and charge separation dynamics, to investigate the relationship between the statistical features of thermal light and the Quinol production in bacterial photosynthesis. This approach allows us to identify a mechanism of photoprotection that relies on charge recombination facilitated by the photon bunching statistics characteristic of thermal sunlight. Our results suggest that the flexible design underpinning natural photosynthesis may therefore rely on exploiting the temporal correlations of thermal light, manifested in photo-bunching patterns, which are preserved for excitations reaching the reaction center.

physics.bio-ph↗

arXiv2016

Exploiting non-trivial spatio-temporal correlations of thermal radiation for sunlight harvesting

The promise of any small improvement in the performance of light-harvesting devices, is sufficient to drive enormous experimental efforts. However these efforts are almost exclusively focused on enhancing the power conversion efficiency with specific material properties and harvesting layers thickness, without exploiting the correlations present in sunlight -- in part because such correlations are assumed to have negligible effect. Here we show, by contrast, that these spatio-temporal correlations are sufficiently relevant that the use of specific detector geometries would significantly improve the performance of harvesting devices. The resulting increase in the absorption efficiency, as the primary step of energy conversion, may also act as a potential driving mechanism for artificial photosynthetic systems. Our analysis presents design guidelines for optimal detector geometries with realistic incident intensities based on current technological capabilities

physics.optics↗