Mesoscale simulation of biomembranes with FreeDTS

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“oblate-to-stomatocyte by volume reduction [57].”

“Also, biological membrane shapes contain information about overall health of an organism, physiological state of the cell and abnormal membrane architectures are implicated in many diseases such as Parkinson’s Disease [3-7].”

“Proteins are one of the main drivers of membrane deformations[45, 46].”

“This process might be relevant for nuclear membrane formation and assembly of nuclear pore complex driven by membrane curvature [54].”

“The non-zero protein-protein interactions lead to a line tension effect at the boundary that can energetically assist the budding process, especially for large protein-protein interactions[51].”

“The third term in equation 9 models proteins that induce membrane curvature through dimerization or oligomerization (see Figure 1-D)[38, 39].”

“Fluid artificial and biological membranes can adapt to a diverse range of morphologies from multispherical structures to the astonishing forms seen in the subcellular organelles such as endoplasmic reticulum, Golgi apparatus, and mitochondria [1, 2].”

“Even without any knowledge of membrane shaping protein structure, DTS simulation can provide some knowledge about their structure by tuning the model parameters against macroscopic biophysical experiments [24, 57].”

“Protein sorting on realistic membranes: Advances in experimental techniques such as cryo-electron tomography now allows for resolving membrane shape of a full organelle or even a cell [2, 55].”

“Also, biological membrane shapes contain information about overall health of an organism, physiological state of the cell and abnormal membrane architectures are implicated in many diseases such as Parkinson’s Disease [3-7].”

“Due to these limitations, FreeDTS does not allow for several membrane-related cellular processes, including membrane fission, fusion and membranes with large holes [59, 60].”

“Also, biological membrane shapes contain information about overall health of an organism, physiological state of the cell and abnormal membrane architectures are implicated in many diseases such as Parkinson’s Disease [3-7].”

“Also, biological membrane shapes contain information about overall health of an organism, physiological state of the cell and abnormal membrane architectures are implicated in many diseases such as Parkinson’s Disease [3-7].”

“Undulation of framed membranes: Flat membranes are a very common and pragmatic model of membrane segments as the curvature of typical cellular or model membranes is small and can be locally considered flat.”

“These phases can recruit membrane proteins which have been postulated to be essential for many biological processes such as signaling and endocytosis[66, 67].”

“The third term in equation 9 models proteins that induce membrane curvature through dimerization or oligomerization (see Figure 1-D)[42, 43].”

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“Protein sorting on realistic membranes: Advances in experimental techniques such as cryo-electron tomography now allows for resolving membrane shape of a full organelle or even a cell [2, 62].”

“Nevertheless, at the mesoscale, the effects of higher order may become significant as cellular membranes often exhibit curvature radii that are comparable to the thickness of the membrane[45, 65].”

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“B shows undulation spectrums for three different flat membranes (1) framed membrane with zero tension and 20% coverage by inclusions (4,5) framed membrane with zero tension confined between two sandwiching walls.”

“Also, biological membrane shapes contain information about overall health of an organism, physiological state of the cell and abnormal membrane architectures are implicated in many diseases such as Parkinson’s Disease [3-7].”

“These phases can recruit membrane proteins which have been postulated to be essential for many biological processes such as signaling and endocytosis[66, 67].”

“It is, however, more challenging for a membrane with open edges, especially since the energy of the edge also depends on the geodesic curvature of the edge [64].”

“2 the local curvature of membranes caused by a single protein or by the assembly of proteins [12-14], membrane shape induced lipid sorting[15], wetting induced membrane deformation [16], and even curvature sensing of proteins[17].”

“Although organelle membranes, such as the ones found in mitochondria and Golgi apparatus, exhibit high-genus topology, there has been only a limited number of studies conducted on membranes with non-spherical topologies, which have considered only simple, low-genus membranes[58-60].”

“Furthermore, the equilibrated output of the FreeDTS can be processed directly by TS2CG to create the system structure with a molecular resolution [27, 28] for full cell or organelle simulations [11, 58].”

“The membranes of cells, however, are much more complex and distinct mechanisms govern their overall arrangement at various scales, ranging from the molecular to the macroscale [8-10].”

“Examples of exciting developments include the local curvature of membranes caused by a single protein or by the assembly of proteins [12-14], membrane shape induced lipid sorting[15], wetting induced membrane deformation [16], and even curvature sensing of proteins[17].”

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“2 the local curvature of membranes caused by a single protein or by the assembly of proteins [12-14], membrane shape induced lipid sorting[15], wetting induced membrane deformation [16], and even curvature sensing of proteins[17].”

“These parameters has physical meaning, Δκ and ΔκG can be seen as an increase the in membrane bending rigidity and gaussian modulus and c0 as a local curvature (for a discussion on this, see [8]).”

“Even without any knowledge of membrane shaping protein structure, DTS simulation can provide some knowledge about their structure by tuning the model parameters against macroscopic biophysical experiments [24, 57].”

“Other mesoscopic model parameters (such as induced local curvature) can be obtained from molecular simulations [37] or from a top-down approach through fitting to experimental data in controlled biophysical experiments [12, 57].”

“, pearling instability [73], which is beyond the capabilities of the current FreeDTS version.”

“Examples of exciting developments include the local curvature of membranes caused by a single protein or by the assembly of proteins [12-14], membrane shape induced lipid sorting[15], wetting induced membrane deformation [16], and even curvature sensing of proteins[17].”

“Pulling a membrane tether: One of the common procedures to deform membranes is pulling a tether (nanotube) using, for example, optical tweezers [12, 47, 48].”

“Theoretical analysis, confirmed by experiment and molecular simulations shows that a free membrane undulation spectrum (with the exception of membranes with small bending rigidities[40]) follows equation 10 [41-44].”

“Nevertheless, at the mesoscale, the effects of higher order may become significant as cellular membranes often exhibit curvature radii that are comparable to the thickness of the membrane[45, 65].”

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“previous works [12, 24, 37, 44] offer a great technology for exploring these processes.”

“In between these two scales, mesoscopic modes in which large biomolecules such as proteins are explicitly considered, while lipids are modeled in a mean field manner (but allows for undulations and shape fluctuations) are needed to fully map out the organization of complex membranes [20, 21].”

“We have described the details of this algorithm in [37] and the SI section 2.”

“Although organelle membranes, such as the ones found in mitochondria and Golgi apparatus, exhibit high-genus topology, there has been only a limited number of studies conducted on membranes with non-spherical topologies, which have considered only simple, low-genus membranes[51-53].”

“processes such as protein clustering via membrane-mediated interaction [22], membrane shape remolding by crowding of intrinsically disordered proteins[23], membrane neck constriction by assembly of proteins [24] and even activity-driven membrane remodeling [25] (for more see [20] and the reference within).”

“In principle, protein density and protein-protein interactions of main membraneshaping proteins can be obtained from experiments such as cross-linking mass spectrometry [56] or from higher-resolution simulations [29].”

“However, it overlooks many phenomena which are the result of membrane fluctuations and rotational and translational entropy of single and (few) proteins[8, 18, 19].”

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“In principle, protein density and protein-protein interactions of main membraneshaping proteins can be obtained from experiments such as cross-linking mass spectrometry [56] or from higher-resolution simulations [29].”

“In between these two scales, mesoscopic modes in which large biomolecules such as proteins are explicitly considered, while lipids are modeled in a mean field manner (but allows for undulations and shape fluctuations) are needed to fully map out the organization of complex membranes [20, 21].”

“The membranes of cells, however, are much more complex and distinct mechanisms govern their overall arrangement at various scales, ranging from the molecular to the macroscale [8-10].”

“FreeDTS also provide a more sophisticated volume coupling through the Jacobus van 't Hoff equation to better model osmotic pressure.”

“FreeDTS allows for controlling global membrane curvature energy to a potential as where 𝑀 = ∑ 2𝐻 𝜐 𝐴 𝜐 𝑁 𝜐 𝜐”

“We have described the details of this algorithm in [35] and the SI section 2.”

“The source code can be found at https://github.com/weria-pezeshkian/FreeDTS.git”

“In addition to its use for exploring many biomembrane application, this software brings us a step closer to simulating realistic biomembranes with molecular resolution.”

“Several mesoscopic models have been used to explore diverse range of membrane associated processes such as protein clustering via membrane-mediated interaction [22], membrane shape remolding by crowding of intrinsically disordered proteins[23], membrane neck constriction by assembly of proteins [24] and even activity-…”

“Pulling a membrane tether: One of the common procedures to deform membranes is pulling a tether (nanotube) using, for example, optical tweezers [12, 54, 55].”

“Several methods are available, each with its own advantages and disadvantages [32, 33].”

“Examples of exciting developments include the local curvature of membranes caused by a single protein or by the assembly of proteins [12-14], membrane shape induced lipid sorting[15], wetting induced membrane deformation [16], and even curvature sensing of proteins[17].”

“Initially, TS2CG was developed for backmapping dynamically triangulated simulation [27, 28] structures into their corresponding coarse-grained (CG) molecular models as an important element for multiscale membrane simulations using, by default, the Martini force field.”

“[186] with the membrane, and assist cells in division [181], membrane budding [81, 182], and the release of viral particles [183].”

“With a flat membrane patch under constant tension, isotropic curvature-inducing inclusions have been shown to produce pearled tubule-like budding when the surface coverage of the proteins exceeds a certain threshold value (28, 29).”

“Proteins in FreeDTS are modeled as inclusions with an in-plane orientation, so that there is at most one inclusion per membrane vertex.”

“The details of the tension-control algorithm can be found elsewhere [20, 37].”

“Similarly, an open source tool was developed to study the effects of nematic interactions used for the analysis of real membranous systems [30].”

“The simulation model uses an internal length scale, 𝑙 )*+ , which can be converted to physical units for the biological system of interest (see below, Methods, and other examples in Ref.”

“26 In contrast to standard DTS simulations of fluid membranes, only vertex displacement moves are allowed in the present model.”

“These discretized models often employ a Monte Carlo scheme to sample the equilibrium configuration of the system [6–8].”

“34 However, studies of membrane deformation that include anisotropic CMCs in combination with the constraint of fixed volume remain poorly understood and to our knowledge, lacking.”