Onsager’s variational principle in soft matter : introduction and application to the dynamics of adsorption of proteins onto fluid membranes

This book is the first collection of lipid-membrane research conducted by leading mechanicians and experts in continuum mechanics. It brings the overall intellectual framework afforded by modern continuum mechanics to bear on a host of challenging problems in lipid membrane physics. These include unique and authoritative treatments of differential geometry, shape elasticity, surface flow and diffusion, interleaf membrane friction, phase transitions, electroelasticity and flexoelectricity, and computational modelling. [Chapter] Lipid bilayers are unique soft materials operating in general in the low Reynolds limit. While their shape is predominantly dominated by curvature elasticity as in a solid shell, their in-plane behavior is that of a largely inextensible viscous fluid. Furthermore, lipid membranes are extremely responsive to chemical stimuli. Because in their biological context they are continuously brought out-of-equilibrium mechanically or chemically, it is important to understand their dynamics. Here, we introduce Onsager’s variational principle as a general and transparent modeling tool for lipid bilayer dynamics. We introduce this principle with elementary examples, and then use it to study the sorption of curved proteins on lipid membranes.Peer ReviewedPostprint (author's final draft

Out-of-equilibrium mechanochemistry and self-organization of fluid membranes interacting with curved proteins

The function of biological membranes is controlled by the interaction of the fluid lipid bilayer with various proteins, some of which induce or react to curvature. These proteins can preferentially bind or diffuse towards curved regions of the membrane, induce or stabilize membrane curvature and sequester membrane area into protein-rich curved domains. The resulting tight interplay between mechanics and chemistry is thought to control organelle morphogenesis and dynamics, including traffic, membrane mechanotransduction, or membrane area regulation and tension buffering. Despite all these processes are fundamentally dynamical, previous work has largely focused on equilibrium and a self-consistent theoretical treatment of the dynamics of curvature sensing and generation has been lacking. Here, we develop a general theoretical and computational framework based on a nonlinear Onsager’s formalism of irreversible thermodynamics for the dynamics of curved proteins and membranes. We develop variants of the model, one of which accounts for membrane curving by asymmetric crowding of bulky off-membrane protein domains. As illustrated by a selection of test cases, the resulting governing equations and numerical simulations provide a foundation to understand the dynamics of curvature sensing, curvature generation, and more generally membrane curvature mechano-chemistry.Peer ReviewedPostprint (author's final draft

An investigation into classroom teachers' perceptions of the value of assessment for formative purposes in secondary schools in Solomon Islands

A key purpose of this qualitative study was to gain an understanding of classroom teachers' perceptions of the value and impact of formative assessment in secondary schools in Solomon Islands. The process of data collection included initial interviews with five classroom teachers selected from four secondary schools in Honiara, Solomon Islands. The interviews were conducted using semistructured interviews with each of the teachers and ended with a focus group conversation. The findings of this study indicated that formative assessment, as a classroom strategy, does have a place in secondary schools in Solomon Islands. Assessment for learning (AfL) is currently employed by these teachers, but the form of formative assessment as reported being used in Solomon Islands secondary school classrooms is limited by policies, systems and methods employed by schools. This study suggests that if classroom teachers are to become effective 'mediators of learning' they must have a better theoretical understanding of social constructivism and metacognition. Otherwise, assessment will always sit outside the process of learning, and classroom teachers and learners will always play traditional rather than contemporary roles in the learning and teaching (and assessment) process. For improvements to be made in areas highlighted in this study, focus must be on teacher knowledge and ability and the policies and practices of schools. Unless teachers, students, parents and policymakers see and value the potential of formative assessment, it will continue to be underemphasized, under-valued and under-used

Out-of-equilibrium mechanochemistry and self-organization of fluid membranes interacting with curved proteins

The function of biological membranes is controlled by the interaction of the fluid lipid bilayer with various proteins, some of which induce or react to curvature. These proteins can preferentially bind or diffuse towards curved regions of the membrane, induce or stabilize membrane curvature and sequester membrane area into protein-rich curved domains. The resulting tight interplay between mechanics and chemistry is thought to control organelle morphogenesis and dynamics, including traffic, membrane mechanotransduction, or membrane area regulation and tension buffering. Despite all these processes are fundamentally dynamical, previous work has largely focused on equilibrium and a self-consistent theoretical treatment of the dynamics of curvature sensing and generation has been lacking. Here, we develop a general theoretical and computational framework based on a nonlinear Onsager’s formalism of irreversible thermodynamics for the dynamics of curved proteins and membranes. We develop variants of the model, one of which accounts for membrane curving by asymmetric crowding of bulky off-membrane protein domains. As illustrated by a selection of test cases, the resulting governing equations and numerical simulations provide a foundation to understand the dynamics of curvature sensing, curvature generation, and more generally membrane curvature mechano-chemistry

Prevention of birth defects in East Africa: A review of national policies

Close to 8 million children are born annually with a serious birth defect, accounting for 5% of all newborn deaths globally. Many birth defects are  associated with folic acid insufficiency, non-communicable diseases (NCDs), teenage or advanced age pregnancies, short birth intervals, and exposure to harmful substances. The majority of countries with the highest birth defects prevalence are in Africa, and the East African Community has made important commitments to improving reproductive, child, and adolescent health and nutrition. The aim of this review was to identify the advances and gaps in national policies addressing birth defect risk factors in the East African Community (Burundi, Kenya, Rwanda, Tanzania, and Uganda) in order to inform additional actions. National laws, regulations and policies were reviewed from the East African Community countries related to grain fortification and supplementation with folic acid; reducing too-early, unwanted and rapid successive pregnancies; and addressing NCDs and exposure to tobacco. All five countries have adopted a policy of mandatory folic acid fortification of wheat and maize flour. However, only in Kenya and Tanzania, are the folic acid levels in line with international recommendations. And, only Uganda has a policy requiring folic acid supplementation administration in the preconceptional period. The East African Community countries have made efforts to reduce too-early, unwanted and rapid successive pregnancies. All countries have banned child marriage and three of five countries have introduced laws to allow  unrestricted access to contraception for adolescents. With regards to promoting prevention and control of NCDs and reducing populations’ exposure, compliance with World Health Organization (WHO) guidelines is limited. Only two countries have developed multi-sectoral policies for NCDs and no countries comply fully with the recommendations of the Framework Convention on Tobacco Control. Much work remains in ensuring  that opportunities for prevention of birth defects are fully realized in the East African Community countries. This review revealed that all countries in the East African Community have, to some extent, adopted policies that are conducive to reducing the risk of birth defects in the region, but significant gaps remain in some key areas of either policy development or implementation. Key words: Congenital abnormalities, Folic acid, Family planning services, Child marriage, Non-communicable Disease

An adaptive finite element method for the modeling of the equilibrium of red blood cells

International audienceThis contribution is concerned with a the numerical modeling of an isolated red blood cell (RBC), and more generally of phospholipid membranes. We propose an adaptive Eulerian finite element approximation, based on the level set method, of a shape optimization problem arising in the study of RBC's equilibrium. We simulate the equilibrium shapes that minimize the elastic bending energy under prescribed constraints of fixed volume and surface area. An anisotropic mesh adaptation technique is used in the vicinity of the cell's membrane to enhance the robustness of the method. Efficient time and spatial discretizations are considered and implemented. We address in detail the main features of the proposed method and finally we report several numerical experiments in the two-dimensional and the three-dimensional axisymmetric cases. The effectiveness of the numerical method is further demonstrated through numerical comparisons with semi-analytical solutions provided by a reduced order model

The plasma membrane as a mechanochemical transducer

Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their environment that is also a biochemical platform, the plasma membrane (PM) is a key interface mediating both cellular response to mechanical stimuli, and subsequent biochemical responses. Here, we review the role of the PM as a mechanosensing structure. We first analyse how the PM responds to mechanical stresses, and then discuss how this mechanical response triggers downstream biochemical responses. The molecular players involved in PM mechanochemical transduction include sensors of membrane unfolding, membrane tension, membrane curvature or membrane domain rearrangement. These sensors trigger signalling cascades fundamental both in healthy scenarios and in diseases such as cancer, which cells harness to maintain integrity, keep or restore homeostasis and adapt to their external environment

Improving awareness of preconception health among adolescents: Experience of a school-based intervention in Lebanon

Background: Maternal behavior before and after conception affects maternal and child health. Limited awareness of adolescents in preconception health may be addressed through school education. The aim of this intervention is to assess preconception health awareness among adolescents in Lebanese high schools and to test the effectiveness of a one-time educational session in improving preconception knowledge. Methods. The intervention consisted of a 30-minute educational session about good practices in preconception health, developed by the National Collaborative Perinatal Neonatal Network's (NCPNN) research team. A convenience sample of high school Lebanese students in grades 10 to 12, aged 14 to 26 years old, from 70 private and public schools in all six Lebanese provinces, participated in the intervention in 2011 and 2012. A multiple-choice questionnaire administered prior to and 2 months after the session was used to assess knowledge improvement among the students. Results: A total of 7,290 students were enrolled. After the session, mean scores of correct answers increased from 4.36 to 6.42 out of 10, representing a 47.2% improvement (p < 0.001). The percent of correct answers increased for all the questions regarding health practices (p < 0.001). The greatest improvement was observed for questions about Trisomy 21, folic acid intake and toxoplasmosis with percentages improvement of 96%, 172% and 83% respectively. Being female or in private school was a significant predictor of higher scores in both pre-test and post-test (p < 0.001). Conclusions: Awareness campaigns in schools increased the preconception health knowledge among high school students. We recommend expanding the scope of this intervention into universities in Lebanon. © 2014Charafeddine et al.; licensee BioMed Central Ltd

Caveolin-1 dolines form a distinct and rapid caveolae-independent mechanoadaptation system.

In response to different types and intensities of mechanical force, cells modulate their physical properties and adapt their plasma membrane (PM). Caveolae are PM nano-invaginations that contribute to mechanoadaptation, buffering tension changes. However, whether core caveolar proteins contribute to PM tension accommodation independently from the caveolar assembly is unknown. Here we provide experimental and computational evidence supporting that caveolin-1 confers deformability and mechanoprotection independently from caveolae, through modulation of PM curvature. Freeze-fracture electron microscopy reveals that caveolin-1 stabilizes non-caveolar invaginations-dolines-capable of responding to low-medium mechanical forces, impacting downstream mechanotransduction and conferring mechanoprotection to cells devoid of caveolae. Upon cavin-1/PTRF binding, doline size is restricted and membrane buffering is limited to relatively high forces, capable of flattening caveolae. Thus, caveolae and dolines constitute two distinct albeit complementary components of a buffering system that allows cells to adapt efficiently to a broad range of mechanical stimuli.We thank R. Parton (Institute for Molecular Biosciences, Queensland), P. Pilch (Boston University School of Medicine) and L. Liu (Boston University School of Medicine) for kindly providing PTRFKO cells and reagents, S. Casas Tintó for kindly providing SH-Sy5y cells, P. Bassereau (Curie Institute, Paris) for kindly providing OT setup, V. Labrador Cantarero from CNIC microscopy Unit for helping with ImageJ analysis, O. Otto and M. Herbig for providing help with RTDC experiments, S. Berr and K. Gluth for technical assistance in cell culture, F. Steiniger for support in electron tomography, and A. Norczyk Simón for providing pCMV-FLAG-PTRF construct. This project received funding from the European Union Horizon 2020 Research and Innovation Programme through Marie Sklodowska-Curie grant 641639; grants from the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033): SAF2014-51876-R, SAF2017-83130-R co-funded by ‘ERDF A way of making Europe’, PID2020-118658RB-I00, PDC2021-121572-100 co-funded by ‘European Union NextGenerationEU/PRTR’, CSD2009- 0016 and BFU2016-81912-REDC; and the Asociación Española Contra el Cáncer foundation (PROYE20089DELP) all to M.A.d.P. M.A.d.P. is member of the Tec4Bio consortium (ref. S2018/NMT¬4443; Comunidad Autónoma de Madrid/FEDER, Spain), co-recipient with P.R.-C. of grants from Fundació La Marató de TV3 (674/C/2013 and 201936- 30-31), and coordinator of a Health Research consortium grant from Fundación Obra Social La Caixa (AtheroConvergence, HR20-00075). M.S.-A. is recipient of a Ramón y Cajal research contract from MCIN (RYC2020-029690-I). The CNIC Unit of Microscopy and Dynamic Imaging is supported by FEDER ‘Una manera de hacer Europa’ (ReDIB ICTS infrastructure TRIMA@CNIC, MCIN). We acknowledge the support from Deutsche Forschungsgemeinschaft through grants to M.M.K. (KE685/7-1) and B.Q. (QU116/6-2 and QU116/9-1). Work in D.N. laboratory was supported by grants from the European Union Horizon 2020 Research and Innovation Programme through Marie Sklodowska-Curie grant 812772 and MCIN (DPI2017-83721-P). Work in C.L. laboratory was supported by grants from Curie, INSERM, CNRS, Agence Nationale de la Recherche (ANR-17-CE13-0020-01) and Fondation ARC pour la Recherche (PGA1-RF20170205456). Work in P.R.-C. lab is funded by the MCIN (PID2019-110298GB-I00), the EC (H20 20-FETPROACT-01-2016-731957). Work in X.T. lab is funded by the MICIN (PID2021-128635NB-I00), ERC (Adv-883739) and La Caixa Foundation (LCF/PR/HR20/52400004; co-recipient with P.R.-C.). IBEC is recipient of a Severo Ochoa Award of Excellence from the MINECO. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MCIN and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).S