Heat production of nerves
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Iwasa K, Tasaki I and Gibbons R.C, 1980.
The propagation of nerve pulses is usually described with the ionic hypothesis, also known as the Hodgkin–Huxley model. In this model the ionic hypothesis describes electrical aspects of the action potential, but it does not provide a theoretical framework for understanding other experimentally observed phenomena associated with nerve pulse propagation such a heat changes or the work performed by variations of mechanical properties.
The research project are focusing on thermodynamic aspects of biological and artificial membranes. Of particular interest is the heat production of nerves during the action potential using thermocouples/temperature sensors on chips in combination with electrical recordings.
1. Gonzalez-Perez A., Budvytyte R., Mosgaard D.L., Nissen S., Heimburg T. Penetration of action potentials during collision in the medial giant axon invertabrates. Phys. Rev. X.,2014; 4:031047.
2. Heimburg T & Jackson AD. On soliton propogation in biomembranes and nerves. PNAS 2005;10:9790-9795.
3. Appali R, van Rienen U and Heimburg T. A comparison of the Hodgkin-Huxley model and the soliton theory for the action potential in nerves. Advances in Planar Lipid Bilayers and Liposomes 2012;16: 275-299.
Artificial tethered phospholipids membranes: development and characterization
Many advances in our understanding of the physical properties, structure, and function of biomembranes have been achieved with membrane mimics such as solid-supported membranes (SSMs) and tethered bilayer lipid membranes (tBLMs). We have developed tBLMs as a long-term stable and versatile experimental model in which thiolated anchor lipids (HC18, WC14 and FC16) span a hydrated layer that separates the membrane from its solid support.
The influence of anchor molecules to properties of tBLM
The assembling strategies of tBLM are mostly depend on the spacer molecules and the type of anchor or layers and the nature of the substrate. Densely packed tether lipids at the surface (no backfilling with βME) typically lead to very high membrane resistances, however this can be a problem to the functional reconstitution of proteins.
To test if the phospholipid mobility is dependent on the nature of the molecular anchor we measured 2D FCS using
tBLMs accomplished on different anchors.
1. McGillivray DJ, Valincius G, Vanderah DJ, Losche M. et.al. Molecular-scale structural and functional characterization of sparsely tethered bilayer lipid membranes, Biointerphases, 2, 21-32 (2007).
2. Budvytyte R , Valincius G, et.al. Anchor Molecules Affect Structure and Properties of Tethered Bilayer Lipid Membranes. Langmuir. 2013. Submitted.
3. Valincius G, Meskauskas T and Ivanauskas F. Langmuir . 2012;28:977-90.
4. Budvytyte R, Mickevicius M, Vanderah DJ, Heinrich F, Valincius G. Modification of tethered bilayer compositions by material exchange with vesicles. Langmuir 2013;29:4320-4327.
The investigation of pore forming toxins interaction with membranes
Geny B and Popoff MR. Biol. Cell (2006) 98, 667–678.
Pore – forming toxins, as the name suggests, disrupt the selective influx and efflux of ions across the plasma membrane by inserting a transmembrane pore. The tBLMs allow monitoring the incorporation and function of channel proteins by changes of their EIS response. In the current study, the PFTs: α-hemolysin (α-HL) from S. aureus , anthrax toxin (PA63) from B. anthracis and cholesterol dependent cytolysin vaginolysin (VLY) from Gardnerella vaginalis were studied using tBLMs designed by us.
1. McGillivray DJ, Valincius G, Heinrich F, Robertson JWF, Vanderah DJ, Febo-Ayala W, Ignatjev I, Losche M, Kasianowicz JJ. Structure of Functional Staphylococcus aureus alpha-Hemolysin Channels in Tethered Bilayer Lipid Membranes. Biophysical Journal 2009;96(4):1547-53.
2. Budvytyte R, Pleckaityte M, Zvirbliene A, Vanderah DJ and Valincius G. Reconstitution and detection of cholesterol dependent vaginolysin into tethered phospholipid bilayers. PlosOne 2013. PloS One, 2013;8(12), e82536. doi:10.1371/journal.pone.0082536.
The study of interaction and neurotoxicity of Aβ1-42 oligomers
Amyloid oligomers are believed to be implicated into the Alzheimer’s pathogenesis. Many different laboratories have reported the effects of amyloid oligomers that were dependent on the size, morphology, toxicity, as well as the methods of preparation or purification. The purpose of the present work is to establish and quantify the dependence of neurotoxic effects on the size and morphology of synthetic Aβ1-42 oligomers also to determine interaction with tBLM. Three different forms of Aβ1-42 aggregates were prepared in vitro. Strong correlation between the size of Ab1–42 oligomers and their toxicity to neuronal cells was observed. The most toxic Ab1–42 oligomeric particles were with the z-heights from 1 to 4 nm measured by AFM.
Interaction of Aβ1-42 aggregates with phospholipid membranes
However, the mechanism by which Aβ1-42 exerts its neurotoxic effect is largely unknown. It may alter the insulating properties of the phospholipid membranes through two mechanisms: ion channel formation and the decrease of the dielectric barrier. The FCS data shows that different size Aβ1-42 oligomers bind differently to the phospholipid membrane.
EIS data indicate that Aβ1–42 affects both the capacitance, and conductance of membrane simultaneously. This suggests that the dielectric damage that alters the ion movement through the membrane barrier may be responsible for the leakage of tBLMs affected Aβ1-42 oligomers.
1. Valincius G., Heinrich F., Budvytyte R., Losche M. et.al. Soluble Amyloid Oligomers Affect Dielectric Membrane Properties by Bilayer Insertion and Domain Formation: Implications for Cell Toxicity, Biophysical Journal, 2008;95:, 4845-4861.
2. Budvytyte R*, Cizas P*, Morkuniene R, Moldovan R, Broccio M, Loesche M, Niaura G, Valincius G, Borutaite V. Size-dependent neurotoxicity of b-amyloid oligomers. Archives of Biochemistry and Biophysics. 2010;496(2):84-92.* These authors contributed equally.
3. Niaura G, Budvytyte R, Kuprionis Z, Valincius G. Sum frequency generation spectroscopy of amyloid fibrils and oligomers at air/water interface. Proc. SPIE, 2010;(7376):1-7.