Membrane Bending Research Articles

A thermodynamic model to predict the minimum energy required for engulfment of linearly aggregated spherical nanoparticles by tubular vesicles

Understanding the interaction of nanoparticles (NPs) with fluid membranes is important to achieve safe and improved performance of NPs in various biomedical applications. Studies show that fluid membranes can drive linear attraction between spherical NPs adsorbed on it, and forms tubular vesicles (membrane tubes) to engulf (wrap) multiple particles. The present work shows the theoretical investigation of the minimum total energy for wrapping of linearly aggregated multiple spherical NPs by a low-tense membrane tube by developing a thermodynamic model that accounts for membrane bending energy, adhesion energy between particles and the membrane, and surface tension energies of the membrane in the low tension regime. The model illustrates that the minimum total energy (negative) decreases with an increasing number of particles undergoing wrapping because of the increasing contact area between the membrane and the particles; resulting in a large adhesion energy gain compensating for the deformation energy costs of the membrane. The large adhesion energy gain results in the spontaneous wrapping and high stability of multiple spherical particles filled in a membrane tube. In addition, the model predicts the critical and the minimum adhesion strength of particles required for the initiation and completion of the wrapping process, respectively. Furthermore, the model demonstrates the wrapped states (non-wrapped, partially wrapped, deeply wrapped, and completely wrapped state) of multiple particles in a membrane tube as a function of the wrapped area of particles. Thus, the developed thermodynamic model provides insights into the understanding of how the spontaneous and simultaneous wrapping of multiple spherical NPs takes place in a low-tense membrane tube.

Admissible shell internal forces and safety assessment of masonry domes

The present paper illustrates a methodology for the safety assessment of masonry domes. The dome is modelled as a thin shell made of a material satisfying Heyman’s hypotheses. Based on the static theorem of limit analysis, the method searches for statically admissible distributions of internal forces within the shell, suitably combining membrane forces and bending moments, by solving a convex optimisation problem. The solution is pursued numerically by means of an expressly developed collocation method that enables obtaining the analytical expressions for each internal force component. In its present formulation the method can be applied to domes of any shape, as well as to arbitrary load distributions. After validation against the benchmark case of the spherical dome under its self-weight, the paper illustrates application of the method to the dome of Pisa Cathedral under vertical loads as a first real case study.

Thermal fluctuations and osmotic stability of lipid vesicles.

Biological membranes constantly change their shape in response to external stimuli, and understanding the remodeling and stability of vesicles in heterogeneous environments is therefore of fundamental importance for a range of cellular processes. One crucial question is how vesicles respond to external osmotic stresses, imposed by differences in solute concentrations between the vesicle interior and exterior. Previous analyses of the membrane bending energy have predicted that micron-sized giant unilamellar vesicles (GUVs) should become globally deformed already for nanomolar concentration differences, in contrast to experimental findings that find deformations at much higher osmotic stresses. In this article, we analyze the mechanical stability of a spherical vesicle exposed to an external osmotic pressure in a statistical-mechanical model, including the effect of thermally excited membrane bending modes. We find that the inclusion of thermal fluctuations of the vesicle shape changes renders the vesicle deformation continuous, in contrast to the abrupt transition in the athermal picture. Crucially, however, the predicted critical pressure associated with global vesicle deformation remains the same as when thermal fluctuations are neglected, approximately six orders of magnitude smaller than the typical collapse pressure recently observed experimentally for GUVs. We conclude by discussing possible sources of this persisting dissonance between theory and experiments.

Unraveling How Cholesterol Affects Multivalency-Induced Membrane Deformation of Sub-100 nm Lipid Vesicles.

Cholesterol plays a critical role in modulating the lipid membrane properties of biological and biomimetic systems and recent attention has focused on its role in the functions of sub-100 nm lipid vesicles and lipid nanoparticles. These functions often rely on multivalent ligand-receptor interactions involving membrane attachment and dynamic shape transformations while the extent to which cholesterol can influence such interaction processes is largely unknown. To address this question, herein, we investigated the attachment of sub-100 nm lipid vesicles containing varying cholesterol fractions (0-45 mol %) to membrane-mimicking supported lipid bilayer (SLB) platforms. Biotinylated lipids and streptavidin proteins were used as model ligands and receptors, respectively, while the localized surface plasmon resonance sensing technique was employed to track vesicle attachment kinetics in combination with analytical modeling of vesicle shape changes. Across various conditions mimicking low and high multivalency, our findings revealed that cholesterol-containing vesicles could bind to receptor-functionalized membranes but underwent appreciably less multivalency-induced shape deformation than vesicles without cholesterol, which can be explained by a cholesterol-mediated increase in membrane bending rigidity. Interestingly, the extent of vesicle deformation that occurred in response to increasingly strong multivalent interactions was less pronounced for vesicles with greater cholesterol fraction. The latter trend was rationalized by taking into account the strong dependence of the membrane bending energy on the area of the vesicle-SLB contact region and such insights can aid the engineering of membrane-enveloped nanoparticles with tailored biophysical properties.

Dynamic Analysis of Cylindrical Shells with Flexoelectric Actuation

The converse flexoelectric effect can be utilized to actuate and control flexible structures. Assessing the precision flexoelectric actuation and control effectiveness of cylindrical shells is the main objective of this study. The application of voltage to the line electrode on the external surface of a flexoelectric patch, coupled with the bottom surface electrode layer, causes an inhomogeneous electric field to be generated, which consequently induces internal actuation stresses. The stress-induced membrane control force and bending control moment generate modal control effects, which regulate the cylindrical shell vibration. For an elastic cylindrical shell with flexoelectric actuation, the modal forces and microscopic behaviors are studied to evaluate the flexoelectric actuation effects. For the transverse direction, the electric field gradient drops sharply with increasing distance from the line electrode; thus, the induced internal actuation stresses concentrate on the upper surface. Due to the inhomogeneous electric field gradient distributions, the membrane control force and bending control moment concentrate like spikes. To evaluate the actuation effects, modal force distributions of the elastic cylindrical shell with flexoelectric actuation are analyzed with respect to design parameters, such as the flexoelectric patch thickness, line-electrode radius, cylindrical shell thickness, and shell radius.

Membrane Bending Enhances Sulfatide Mediated Sickle Mature Erythrocyte Adhesion

Introduction: Abnormal red blood cell (RBC) adhesion due to polymerization of sickle hemoglobin (HbS) is central to the pathophysiology of SCD. Early erythrocytes (reticulocytes), expanded in number due to sustained stress erythropoiesis stimulated by anemia and hypoxia, are more adhesive to vascular endothelial proteins and surfaces than are mature erythrocytes. However, mature erythrocytes typically constitute >80% of all RBCs in SCD, and the relative contribution made by erythrocytes vs. reticulocytes to acute and chronic vasculopathy is not well understood. We hypothesized that sphingomyelinase (SMase) activity that is upregulated by accumulated bending energy leads to elevated membrane sulfatide availability and thus hypoxic mature erythrocyte adhesion under hypoxia. Methods: We probed the adhesion of RBCs obtained from SCD patients (#NCT02824471) stained with acridine orange under various physiological conditions in microchannels that were coated with laminin. Then we analyzed the morphology of single sickle reticulocytes and mature erythrocytes to estimate the membrane bending energy. Results and Discussion: We found that mature erythrocyte adhesion to laminin in controlled microfluidic experiments is significantly greater under hypoxia than under normoxia (1856±481 vs. 78±23, mean±SEM), while sickle reticulocyte adhesion, high to begin with, does not change (1281 ±299 vs. 1258±328, mean±SEM). Furthermore, we show that among the adherent RBCs, mature erythrocytes have greater elongation and accumulated membrane bending energy compared to reticulocytes under hypoxia (Figure 1A). Accumulated membrane bending is known to elicit SMase, and laminin establishes highly specific bonds with sulfatides which are downstream of the SMase. These results suggest that SMase is likely elicited particularly in sickle mature erythrocytes, which become highly adhesive with deoxygenation. This is likely due to loss of membrane surface area with RBC maturation, which may be excessive in SCD due to membrane vesiculation and microparticle release. To elucidate the roles of SMase and sulfatide in the adhesion of mature erythrocytes, we repeated the adhesion experiments with SMase and anti-sulfatide incubation. We found that SMase increases the hypoxia-enhanced adhesion of mature erythrocytes and the anti-sulfatide antibody inhibits the enhanced adhesion of mature erythrocytes seen under hypoxia (Figure 1B). Collectively, these data demonstrate the effect of accumulated membrane damage on the abnormal adhesion of sickle mature erythrocytes. Conclusions: Patient-to-patient variability in hypoxia enhanced mature erythrocyte adhesion suggests a role in modulating clinical comorbidities and or genetic polymorphisms relevant to red cell health and hypoxic regulation. These results also implicate the lipid components of the plasma membrane in the pathophysiology of RBC dysfunction in SCD. Therefore, sulfatide and the components of its pathway, such as SMase, could be explored as potential therapeutic targets to inhibit sickle erythrocyte adhesion in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

An adaptive triangular element of absolute nodal coordinate formulation for thin plates and membranes

An adaptive triangular element based on the absolute nodal coordinate formulation is developed for thin plates and membranes in this work. An elegant theory for thin plate and membrane is first generated under the Kirchhoff–Love assumptions, where the Green strain tensor is decomposed into membrane strain and bending strain tensors. The Hsieh–Clough–Tocher triangular element is extended into the frame of the absolute nodal coordinate formulation for the first time and corresponding shape functions are then derived. The elastic force and Jacobian matrix of the membrane element are explicitly derived by the multiplication of constant tensors and generalized coordinates, resulting in higher efficiency than the plate element. The same group of generalized coordinates is used in membrane and plate elements. Based on this characteristic, a novel adaptive algorithm is proposed based on the stress states to determine at which Gauss points only the membrane strain needs to be considered. The accuracy and adaptability are validated using several benchmark problems. The present adaptive element can improve efficiency without loss of accuracy in cases where most of the membrane is fully tensioned and a part of the local region is slack or wrinkled.

Mechanics of diffusion-mediated budding and implications for virus replication and infection.

Budding allows virus replication and macromolecular secretion in cells through the formation of a membrane protrusion (bud) that evolves into an envelope. The largest energetic barrier to bud formation is membrane deflection and is trespassed primarily thanks to nucleocapsid-membrane adhesion. Transmembrane proteins (TPs), which later form the virus ligands, are the main promotors of adhesion and can accommodate membrane bending thanks to an induced spontaneous curvature. Adhesive TPs must diffuse across the membrane from remote regions to gather on the bud surface, thus, diffusivity controls the kinetics. This paper proposes a simple model to describe diffusion-mediated budding unravelling important size limitations and size-dependent kinetics. The predicted optimal virion radius, giving the fastest budding, is validated against experiments for coronavirus, HIV, flu and hepatitis. Assuming exponential replication of virions and hereditary size, the model can predict the size distribution of a virus population. This is verified against experiments for SARS-CoV-2. All the above comparisons rely on the premise that budding poses the tightest size constraint. This is true in most cases, as demonstrated in this paper, where the proposed model is extended to describe virus infection via receptor- and clathrin-mediated endocytosis, and via membrane fusion.

Bending Elasticity of Phospholipid Bilayers Containing an Amphipathic Peptide with Low Mammalian Cytotoxicity


 
 
 Peptide mimetics imitate natural peptides’ structure but they could be specifically designed to be more selective concerning their toxicity to mammalian cells. In most cases this specificity is due to their ability to form α-helix in amphipathic environment. In addition, the specific activity depends on the ability of final structure to penetrate cell membrane. Being responsible for the cell integrity and compartmentalization, biomembranes also play a major role in cellular processes, in which the membrane deformations are important. In the present study we probe peptide-membrane interactions for a shortened amino acid sequence KLAKLAK-NH2 of an antimicrobial peptide with apoptotic effect. The bending rigidity of model lipid bilayers is measured by flicker spectroscopy of quasispherical unilamellar vesicles monitored and analyzed in phase contrast light microscopy. At high peptide concentrations ∼ 30 μmol/L and peptide-to-lipid total molar ratios ∼ 0.90 bilayer stacking formation is observed. A reduction of the bending constant is reported at peptide-to-lipid total molar ratio ∼ 0.80. The membrane softening indicates peripheral peptide orientation at the lipid bilayer, which is considered a prerequisite for channel formation. Based on KLAKLAK-NH2 effect on the membrane bending elasticity we provide an evaluation of the peptide partition coefficient characterizing its affinity to POPC bilayers. The acquired results might be helpful in efforts to further tailor the pharmacokinetic properties of antimicrobial peptides in combination with strengthened stability towards enzymatic degradation.
 
 

Indentation of pore-spanning lipid membranes: Spring-stiffening or -softening responses and apparent stiffness prediction

Atomic force microscopy (AFM)-based nanoindentation has emerged as a key nanomechanical mapping method to probe mechanical properties of two-dimensional engineering and biological materials. In comparison with extensive analytical studies on the indentation of freestanding solid thin films, surprisingly little attention has been drawn on analytical predictions of mechanical responses of freestanding lipid membranes to indentation in the framework of Helfrich membrane theory. Here we perform systematic theoretical studies with formulated analysis on indentation of nanopore-spanning lipid membranes. Two types of lipid membranes are considered. One is the membrane subject to uniform area stretching and the membrane is found to exhibit a spring-stiffening behavior during indentation, while the other is the membrane of constant tension and a spring-softening behavior at intermediate indentation is exhibited. The smaller the membrane tension is, the clearer the spring-softening feature is. For both types of membranes, analytical solutions of load–depth relationship at small indentation and apparent membrane stiffnesses are obtained at small and large tension. For the stretched lipid membranes, a cubic nonlinearity arising from membrane stretching is specified. Roles of membrane bending rigidity, (pre-)tension, or area compression modulus, and indenter size in membrane indentation are elucidated. Moreover, pressure of contact between the membrane and indenter and a line load of contact acting along the contact edge are obtained based on the shell theory. Our results provide fundamental insights on nonlinear mechanical behaviors of the lipid membrane indentation.

Phase separation and critical size in molecular sorting.

Molecular sorting is a fundamental process that allows eukaryotic cells to distill and concentrate specific chemical factors in appropriate cell membrane subregions, thus endowing them with different chemical identities and functional properties. A phenomenological theory of this molecular distillation process has recently been proposed [M. Zamparo, D. Valdembri, G. Serini, I.V. Kolokolov, V.V. Lebedev, L. Dall'Asta, and A. Gamba, Phys. Rev. Lett. 126, 088101 (2021)0031-900710.1103/PhysRevLett.126.088101], based on the idea that molecular sorting emerges from the combination of (a) phase separation driven formation of sorting domains and (b) domain-induced membrane bending, leading to the production of submicrometric lipid vesicles enriched in the sorted molecules. In this framework, a natural parameter controlling the efficiency of molecular distillation is the critical size of phase separated domains. In the experiments, sorting domains appear to fall into two classes: unproductive domains, characterized by short lifetimes and low probability of extraction, and productive domains, that evolve into vesicles that ultimately detach from the membrane system. It is tempting to link these two classes to the different fates predicted by classical phase separation theory for subcritical and supercritical phase separated domains. Here, we discuss the implication of this picture in the framework of the previously introduced phenomenological theory of molecular sorting. Several predictions of the theory are verified by numerical simulations of a lattice-gas model. Sorting is observed to be most efficient when the number of sorting domains is close to a minimum. To help in the analysis of experimental data, an operational definition of the critical size of sorting domains is proposed. Comparison with experimental results shows that the statistical properties of productive and unproductive domains inferred from experimental data are in agreement with those predicted from numerical simulations of the model, compatibly with the hypothesis that molecular sorting is driven by a phase separation process.

Membrane attachment and fusion of HIV-1, influenza A, and SARS-CoV-2: resolving the mechanisms with biophysical methods.

Attachment to and fusion with cell membranes are two major steps in the replication cycle of many human viruses. We focus on these steps for three enveloped viruses, i.e., HIV-1, IAVs, and SARS-CoV-2. Viral spike proteins drive the membrane attachment and fusion of these viruses. Dynamic interactions between the spike proteins and membrane receptors trigger their specific attachment to the plasma membrane of host cells. A single virion on cell membranes can engage in binding with multiple receptors of the same or different types. Such dynamic and multivalent binding of these viruses result in an optimal attachment strength which in turn leads to their cellular entry and membrane fusion. The latter process is driven by conformational changes of the spike proteins which are also class I fusion proteins, providing the energetics of membrane tethering, bending, and fusion. These viruses exploit cellular and membrane factors in regulating the conformation changes and membrane processes. Herein, we describe the major structural and functional features of spike proteins of the enveloped viruses including highlights on their structural dynamics. The review delves into some of the case studies in the literature discussing the findings on multivalent binding, membrane hemifusion, and fusion of these viruses. The focus is on applications of biophysical tools with an emphasis on single-particle methods for evaluating mechanisms of these processes at the molecular and cellular levels.

Cholesterol Stiffening of Lipid Membranes.

Biomembrane order, dynamics, and other essential physicochemical parameters are controlled by cholesterol, a major component of mammalian cell membranes. Although cholesterol is well known to exhibit a condensing effect on fluid lipid membranes, the extent of stiffening that occurs with different degrees of lipid acyl chain unsaturation remains an enigma. In this review, we show that cholesterol locally increases the bending rigidity of both unsaturated and saturated lipid membranes, suggesting there may be a length-scale dependence of the bending modulus. We review our published data that address the origin of the mechanical effects of cholesterol on unsaturated and polyunsaturated lipid membranes and their role in biomembrane functions. Through a combination of solid-state deuterium NMR spectroscopy and neutron spin-echo spectroscopy, we show that changes in molecular packing cause the universal effects of cholesterol on the membrane bending rigidity. Our findings have broad implications for the role of cholesterol in lipid–protein interactions as well as raft-like mixtures, drug delivery applications, and the effects of antimicrobial peptides on lipid membranes.Graphical

Biomechanical Role of Epsin in Influenza A Virus Entry.

Influenza A virus (IAV) utilizes clathrin-mediated endocytosis for cellular entry. Membrane-bending protein epsin is a cargo-specific adaptor for IAV entry. Epsin interacts with ubiquitinated surface receptors bound to IAVs via its ubiquitin interacting motifs (UIMs). Recently, epsin was shown to have membrane tension sensitivity via its amphiphilic H0 helix. We hypothesize this feature is important as IAV membrane binding would bend the membrane and clinical isolates of IAVs contain filamentous IAVs that may involve more membrane bending. However, it is not known if IAV internalization might also depend on epsin’s H0 helix. We found that CALM, a structurally similar protein to epsin lacking UIMs shows weaker recruitment to IAV-containing clathrin-coated structures (CCSs) compared to epsin. Removal of the ENTH domain of epsin containing the N-terminus H0 helix, which detects changes in membrane curvature and membrane tension, or mutations in the ENTH domain preventing the formation of H0 helix reduce the ability of epsin to be recruited to IAV-containing CCSs, thereby reducing the internalization of spherical IAVs. However, internalization of IAVs competent in filamentous particle formation is not affected by the inhibition of H0 helix formation in the ENTH domain of epsin. Together, these findings support the hypothesis that epsin plays a biomechanical role in IAV entry.

Solitons in the Heimburg-Jackson model of sound propagation in lipid bilayers are enabled by dispersion of a stiff membrane.

Experiments show that elastic constants of lipid bilayers vary greatly during the liquid-to-gel phase transition. This fact forms the cornerstone of the Heimburg-Jackson model of soliton propagation along membranes of axons, in which the action potential is accompanied by a traveling phase transition. However, the dispersion term, which is crucial for the existence of solitons, is added to the Heimburg-Jackson model ad hoc and set to fit experimental observations. In the present paper, we aim to consolidate this view with continuous membrane mechanics. Using literature data, we show that the compression modulus of a DPPC membrane is smaller by approximately an order of magnitude during phase transition. With a series expansion of the compression modulus, we write the action of a membrane and solve the corresponding wave equation analytically using an Exp-function method. We confirm that membrane solitons with speeds around 200 m/s are possible with amplitudes inversely proportional to their speed. We conclude that dispersion necessary for existence of solitons is directly related to a membrane's bending properties, offering a possible explanation for h. Our findings are in general agreement with existing literature and give insight into a general mechanism of wave propagation in membranes close to transition.

Amphiphysin AoRvs167-Mediated Membrane Curvature Facilitates Trap Formation, Endocytosis, and Stress Resistance in Arthrobotrys oligospora.

Bin1/Amphiphysin/Rvs (BAR) domain-containing proteins mediate fundamental cellular processes, including membrane remodeling and endocytosis. Nematode-trapping (NT) fungi can differentiate to form trapping structures through highly reorganized cell membranes and walls. In this study, we identified the NT fungus Arthrobotrys oligospora ortholog of yeast Rvs167 and documented its involvement in membrane bending and endocytosis. We further confirmed that the deletion of AoRvs167 makes the fungus more hypersensitive to osmotic salt (Nacl), higher temperatures (28 to 30 °C), and the cell wall perturbation agent Congo red. In addition, the disruption of AoRvs167 reduced the trap formation capacity. Hence, AoRvs167 may regulate fungal pathogenicity through the integrity of plasma membranes and cell walls.

Effect of Slp4-a on Membrane Bending During Prefusion of Vesicles in Blood-Brain Barrier.

Vesicle exocytosis is a promising pathway for brain drug delivery through the blood-brain barrier to treat neurodegenerative diseases. In vesicle exocytosis, the membrane fusion process is initiated by the calcium sensor protein named synaptotagmin-like protein4-a (Slp4-a). Understanding conformational changes of Slp4-a during the prefusion stage of exocytosis will help to develop vesicle-based drug delivery to the brain. In this work, we use molecular dynamics (MD) simulations with a hybrid force field coupling united-atom protein model with MARTINI coarse-grained (CG) solvent to capture the conformational changes of Slp4-a during the prefusion stage. These hybrid coarse-grained simulations are more efficient than all-atom MD simulations and can capture protein interactions and conformational changes. Our simulation results show that the calcium ions play critical roles during the prefusion stage. Only one calcium ion can remain in each calcium-binding pocket of Slp4-a C2 domains. The C2B domain of calcium-unbound Slp4-a remains parallel to the endothelial membrane, while the C2B domain of calcium-bound Slp4-a rotates perpendicular to the endothelial membrane to approach the vesicular membrane. For the calcium-bound case, three Slp4-a proteins can effectively bend lipid membranes at the prefusion stage, which could later trigger lipid stalk between membranes. This work provides a better understanding how C2 domains of Slp4-a operate during vesicle exocytosis from an endothelial cell.

The bending rigidity of the red blood cell cytoplasmic membrane.

An important mechanical property of cells is the membrane bending modulus, κ. In the case of red blood cells (RBCs) there is a composite membrane consisting of a cytoplasmic membrane and an underlying spectrin network. Literature values of κ are puzzling, as they are reported over a wide range, from 5 kBT to 230 kBT. To disentangle the contribution of the cytoplasmic membrane from the spectrin network, we investigated the bending of red blood cell cytoplasmic membranes (RBCcm) in the absence of spectrin and adenosine triphosphate (ATP). We used a combination of X-ray diffuse scattering (XDS), neutron spin-echo (NSE) spectrometry and Molecular Dynamics (MD) simulations. Our results indicate values of κ of order 4 kBT to 6 kBT, relatively small compared to literature values for most single component lipid bilayers. We suggest two ways this relative softness might confer biological advantage.

A three‐phase laminated anisotropic elliptical inhomogeneity with internal uniform stress resultants

AbstractWe use the Stroh octet formalism for the coupled stretching and bending deformations of Kirchhoff laminated anisotropic thin plates together with the complex variable formulations of the decoupled stretching and bending deformations of Kirchhoff homogeneous isotropic thin plates to study the internal stress resultants inside a laminated anisotropic elliptical inhomogeneity bonded to a surrounding infinite laminated anisotropic matrix through a confocal interphase layer composed of a homogeneous isotropic plate when the matrix is subjected to uniform remote membrane stress resultants and bending moments. We prove that for given geometric and material parameters of the composite, the internal stress resultants inside the elliptical inhomogeneity are uniform when four specific conditions on the remote loading are satisfied. Furthermore, the internal uniform elastic field is determined in real‐form in terms of the two 8 × 8 fundamental elastic plate matrices for both the inhomogeneity and the matrix and the three 4 × 4 real matrices S, H, and L for the matrix.

Deployment and surface accuracy of regularly creased membranes

Creases are highly localized regions ubiquitous across different length scales in low-dimensional natural and engineering systems. Their presence strongly influences the mechanical response and surface accuracy of creased membrane materials and structures. In this paper, we study the deployment of folded sheets composed of an arbitrary number of non-interacting and parallel creases. We develop a mathematical formulation that describes the nonlinear mechanics of systematically creased membranes composed of a single or multiple folds, and predicts their surface accuracy during unfolding. The proposed solution shows the contribution of membrane bending and crease energies during deployment, and reveals the presence of two dimensionless parameters that govern the unfolding behaviour. Sensitivity analyses are also performed to assess the influence of the crease geometry and constitutive behaviour. The analytical predictions are validated through finite element analyses and deployment tests performed on thin films with one, two and three fold lines, where imaging techniques are employed to quantify deformation. The excellent agreement between theoretical and experimental results testifies that the developed formulation represents a precise tool to assess the tensioning of creased membranes, with applications ranging from origami metamaterials to lightweight space structures where precise shape control is paramount.