We are pleased to announce the publication of a new research article entitled “Stiffening cells with light”, resulting from a collaboration with Julien Husson at École Polytechnique.

Summary: Fluorescence microscopy is commonly used to observe living cells and organisms, but it can induce phototoxicity, which may lead to erroneous interpretations. The primary cause of phototoxic cell damage is the production of reactive oxygen species (ROS), which can crosslink intracellular proteins and nucleic acids. Using profile microindentation and atomic force microscopy, we demonstrate that excitation of various fluorescent probes causes a rapid dose-dependent increase in cell stiffness across multiple cell types. This photostiffening effect explains why T cells loaded with the Fluo-4 calcium probe stop protruding within seconds after light excitation. We show that upon fluorophore excitation, ROS production is correlated with increased stiffness, and we reproduce the effect by incubating cells with H₂O₂ or the photosensitizer pheophorbide a. This study underscores the importance of controls and proposes photostiffening as a method for quantifying phototoxicity.

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Image credits: Julien Husson. Cover image from Cell Reports Physical Science.

Coccidian parasites can rely on their mechanical properties to infect their hosts. Here, we detail a microindentation-based technique for quantifying the wall mechanics of coccidian oocysts. We describe steps for micropipette fabrication, calibration of flexible microindenters, system assembly, and quantifying indentation and rupture forces. We then present procedures for automated data analysis using open-source software and programming languages. The protocol enables measurement of wall rupture forces and is applicable to study the integrity of parasites under various physiological conditions.

https://doi.org/10.1016/j.xpro.2025.104234

A new commentary has been published in the EMBO journal called “Unraveling T-cell decoding strategy : a step forward” by Philippe Robert & Pierre Bongrand.

This invited commentary provided us with an opportunity to summarize the present stage of a long-term quest for the unraveling of T lymphocyte decision-making after encountering a foreign antigen.
This problem is of both practical and theoretical importance. Firstly, understanding cell behavior is a major challenge for cell biologists and this active research field involves “omic” approaches, biophysics, and theoretical modeling with or without artificial intelligence tools. Secondly, the growing importance of immunotherapy is dependent on the choice of target antigens used for immunization or Car-T-cells generation.

A number of reports published three decades ago strongly supported the view that T cell decision could be predicted by conventional descriptors of the interaction between T cell receptors and antigen ligands, such as affinity constants or kinetic rates measured on soluble ligands and recepors. However, despite a general agreement with experience, some discrepancies remained.

During the following years, studies performed at the single molecule level by a number of biophysically oriented teams, including LAI investigators, clearly demonstrated that aforementioned descriptors did not satisfactorily account for the interactions between membrane-bound molecules, due to the influence of mechanical forces, intervening molecules, and limitation of molecular motions. A number of experimental reports suggested that aforementioned discrepancies could be due to mechanical effects.

In the current issue of the Embo Journal, a report suggests that these discrepancies between T cell activation and measured affinity constant were in fact due to a faulty affinity determination. The authors conclude that the conventional affinity constant may be the best predictor of T cell decision.

We suggested in our commentary that this important result was not in contradiction with the current view that the detailed mechanisms of T cell activation are dependent on the fine properties of ligand binding and that further studies are needed to build an exhaustive model of the activation process.

https://doi.org/10.1038/s44318-025-00645-4

Figure 1. Difficulty of comparing 2D and 3D molecule association.

(A) Conventional 3D molecular binding. Molecular encounters are well-described by standard diffusion equations. Molecular translation and rotation are weakly dependent on molecular size and shape. Bond rupture is driven by thermal fluctuations. The association rate (k_on), dissociation rate (k_off), and affinity constant (K_a) are thus determined by molecular structure and generic mechanisms, they may thus be considered as intrinsic properties of interacting molecules A and B. (B) 2D association. When ligand and receptor molecules are bound to surfaces, the frequency of encounters is strongly dependent on the distance d beteween surfaces, surface roughness, flexibility of the anchors of binding sites that drive molecular contact frequency and relative molecule orientation, lateral diffusion of anchored molecules, and possible role of bulk repeller molecules (r) on surfaces. (C) 2D dissociation. Bond rupture is strongly dependent on the intensity and time-dependence of forces exerted on the bonds. When a bond is broken, the dynamics of anchoring surfaces may influence rebinding.

Coccidian parasite can withstand a wide range of chemical and physical factors, contributing to their food- and water-borne transmission to humans worldwide. Eimeria acervulina has been proposed as a non-human pathogenic alternative of Toxoplasma gondii to assess food and water decontamination, however it is not known whether the two parasites exposed to chemical and thermal treatments parallel in terms of oocyst structure and infectivity. Using bioassays and lectin-based assays combined with flow cytometry and fluorescence microscopy analyses, this study shows that E. acervulina and T. gondii oocysts display similar response to heating and/or freezing and bleach or NaOH treatments, as in maintaining infectivity, with E. acervulina oocysts retaining their size and structure better than T. gondii. Collectively, these results suggest that E. acervulina is a reliable model for studying the response of T. gondii oocysts to certain chemical and physical agents.

https://doi.org/10.1016/j.exppara.2025.109049

Understanding the transport and retention of Toxoplasma gondii oocysts through soils and into ground and surface water is essential for determining the risk this parasite poses to water resources and human health worldwide. We studied here how various naturally occurring groundwater solutions containing different types of organic compounds (fulvic and humic acids) and electrolytes (NaCl, MgCl₂, CaCl₂) at different concentrations can affect the transport and retention of oocysts in engineered-saturated silica sand columns subjected to continuous flow to simulate the movement of groundwater through an aquifer. Breakthrough curve results from the qPCR analysis were then compared to non-reactive tracer tests to determine parameters that govern the transport of oocysts in saturated porous media. Though breakthrough of oocysts was observed in all tested solutions, higher ionic strength and ion valency resulted in greater oocyst retention. When both organic matter and electrolyte solutions were added to the systems, the electrolyte solutions displayed a far greater influence on parasite retention when compared to the influence of the organic matter alone. Collectively, this study demonstrates the pivotal role of soil groundwater solution chemistry in both the transport and retention of this important zoonotic parasite

https://doi.org/10.1371/journal.pone.0331812