Laskennallinen tutkimus missing-in-metastasis'in mekanismista muovata solukalvoa

Missing-in-metastasis (MIM) is an adaptor protein that connects the actin cytoskeleton to the plasma membrane. Its N-terminal domain, known as MIM IMD, is a member of the Bin-amphiphysin-Rvs (BAR) domain family, known for their ability to generate membrane curvature. More specifically, it is an inverse BAR (I-BAR) domain, generating negative curvature. MIM IMD is implicated in the formation of lamellipodia and filopodia, disassembly of actin stress fibers, and maintenance of adherence junctions. However, the exact membrane sculpting mechanism it employs has remained elusive. So far MIM has been studied only experimentally. In this thesis, for the first time we employ molecular dynamics (MD) simulations to computationally address the membrane sculpting mechanism of MIM. We employ both atomistic and mesoscopic scale simulations, examining the behaviour of MIM IMD in the presence of lipid bilayers of different properties. First, inspection of the crystal structure of the domain under study revealed that it cannot generate negative curvature by simply imposing its intrinsic curvature on the membrane. Introducing dynamics, we found that MIM IMD is actually considerably more flexible as compared to other BAR domains. Moreover, we discovered that MIM IMD can acquire a positive conformation, which may enable its suggested ability to sense and couple with positive membrane curvature. However, our study does not support the proposition that it would sense curvature via inserting its N-terminal amphipathic helix to a membrane. Additionally, our study reveals that significant protein-lipid interactions between the domain and lipids are driven by electrostatic interactions, which further induce clustering of phosphatidylinositol 4,5-biphosphate (PI(4,5)P2). We suggest the PI(4,5)P2-clustering may have a significant role in the curvature generation mechanism, due to increase of membrane fluidity

Vital Sign Monitoring Using FMCW Radar in Various Sleeping Scenarios

Remote monitoring of vital signs for studying sleep is a user-friendly alternative to monitoring with sensors attached to the skin. For instance, remote monitoring can allow unconstrained movement during sleep, whereas detectors requiring a physical contact may detach and interrupt the measurement and affect sleep itself. This study evaluates the performance of a cost-effective frequency modulated continuous wave (FMCW) radar in remote monitoring of heart rate and respiration in scenarios resembling a set of normal and abnormal physiological conditions during sleep. We evaluate the vital signs of ten subjects in different lying positions during various tasks. Specifically, we aim for a broad range of both heart and respiration rates to replicate various real-life scenarios and to test the robustness of the selected vital sign extraction methods consisting of fast Fourier transform based cepstral and autocorrelation analyses. As compared to the reference signals obtained using Embla titanium, a certified medical device, we achieved an overall relative mean absolute error of 3.6% (86% correlation) and 9.1% (91% correlation) for the heart rate and respiration rate, respectively. Our results promote radar-based clinical monitoring by showing that the proposed radar technology and signal processing methods accurately capture even such alarming vital signs as minimal respiration. Furthermore, we show that common parameters for heart rate variability can also be accurately extracted from the radar signal, enabling further sleep analyses.publishedVersionPeer reviewe

Laskennallinen tutkimus missing-in-metastasis'in mekanismista muovata solukalvoa

Missing-in-metastasis (MIM) is an adaptor protein that connects the actin cytoskeleton to the plasma membrane. Its N-terminal domain, known as MIM IMD, is a member of the Bin-amphiphysin-Rvs (BAR) domain family, known for their ability to generate membrane curvature. More specifically, it is an inverse BAR (I-BAR) domain, generating negative curvature. MIM IMD is implicated in the formation of lamellipodia and filopodia, disassembly of actin stress fibers, and maintenance of adherence junctions. However, the exact membrane sculpting mechanism it employs has remained elusive. So far MIM has been studied only experimentally. In this thesis, for the first time we employ molecular dynamics (MD) simulations to computationally address the membrane sculpting mechanism of MIM. We employ both atomistic and mesoscopic scale simulations, examining the behaviour of MIM IMD in the presence of lipid bilayers of different properties. First, inspection of the crystal structure of the domain under study revealed that it cannot generate negative curvature by simply imposing its intrinsic curvature on the membrane. Introducing dynamics, we found that MIM IMD is actually considerably more flexible as compared to other BAR domains. Moreover, we discovered that MIM IMD can acquire a positive conformation, which may enable its suggested ability to sense and couple with positive membrane curvature. However, our study does not support the proposition that it would sense curvature via inserting its N-terminal amphipathic helix to a membrane. Additionally, our study reveals that significant protein-lipid interactions between the domain and lipids are driven by electrostatic interactions, which further induce clustering of phosphatidylinositol 4,5-biphosphate (PI(4,5)P2). We suggest the PI(4,5)P2-clustering may have a significant role in the curvature generation mechanism, due to increase of membrane fluidity