During development, neurons initiate a maturation process during which they start expressing voltage-gated ion channels, form synapses, and start communicating via action potentials. Little is known about external factors regulating this process. Here, we identify environmental mechanics as an important regulator of neuronal maturation, and a molecular pathway linking tissue stiffness to this process. Using patch clamp electrophysiology, calcium imaging and immunofluorescence, we find that, in stiffer environments, neurons show a delay in voltage-gated ion channel activity, action potentials, and synapse formation. RNA sequencing and CRISPR/Cas9 knockdown reveal that the mechanosensitive ion channel Piezo1 supresses transthyretin expression on stiffer substrates, slowing down electrical maturation. In Xenopus laevis embryos, brain stiffness negatively correlates with synapse density, and artificial tissue stiffening delays synaptic activity in vivo. Our data indicate that environmental stiffness represents a fundamental regulator of neuronal maturation, critical for brain circuit development and potentially for neurodevelopmental disorders.

Thermodynamics is a theory based on phenomenological premises and has wide applicability in science and technology. However, it remains one of the most challenging subjects to understand and teach, which makes it an excellent candidate for research and development of teaching methods. In this research, a questionnaire was used to evaluate the current knowledge of Bachelor’s and Master’s physics students, analyzing their immediate understanding of the topic and exploring their reasoning and thought processes. The questionnaire is divided into three sections which sequentially examine high school knowledge of entropy and thermodynamics; understanding of (ir)reversible processes related to energy and entropy change; and the distinction between equilibrium and nonequilibrium states. Based on the analysis of the results, we identified difficulties in understanding and articulating and applying the learned concepts. In particular, misunderstandings of entropy changes in isothermal processes and isolated systems are observed among students at all levels. Additionally, students find it difficult to distinguish between the contributions of energy and entropy changes to a system and its environment in the processes. The difficulty in defining (non)equilibrium states is present among Bachelor’s second-year physics students. To address these challenges, we propose adjustments to the teaching approach, including discussions about entropy sources and process (ir)reversibility, incorporating more theoretical and everyday examples of various processes and (non)equilibrium states and allowing more time for student discussions.

The glycocalyx is a complex layer of glycosylated biomolecules surrounding all cells in the human body. It is involved in the regulation of critical cellular processes such as immune response modulation, cell adhesion, and host-pathogen interactions. Despite these insights, the functional relationship between glycocalyx architecture and cellular state has remained elusive so far, mainly attributable to the structural diversity of glycocalyx constituents and their nanoscale organization. Here, we show that DNA-tagged lectin labeling and metabolic oligosaccharide engineering enables multiplexed super-resolution microscopy of glycocalyx constituents, yielding an atlas of glycocalyx architecture with nanometer resolution. Quantitative analysis of the obtained nanoscale map of glycocalyx constituents facilitates the extraction of characteristic spatial relationships that accurately report on cellular state. We demonstrate the capacity of our approach, which we term Glycan Atlassing, across cell and tissue types, ranging from cultured cell lines to primary immune cells, neurons, and primary patient tissue. Glycan Atlassing establishes a powerful strategy for investigating glycocalyx remodeling in development and disease, potentially enabling the development of new glycocalyx-centered targets in diagnosis and therapy.