From modeling nanoparticlemembrane interaction towards toxicology

Transcription

1 Rafi Korenstein, Tel Aviv Oded Maimon, Tel Aviv Emilio Benfenati, Milan Gerhard Gompper, Jülich From modeling nanoparticlemembrane interaction towards toxicology 2 October 2015 Karandeep Singh, Sabyasachi Dasgupta, Qingfen Yu, Thorsten Auth, and Gerhard Gompper Theoretical Soft Matter and Biophysics Forschungszentrum Jülich

2 H. Noguchi, J. Phys. Soc. Jpn. 78, (2009) Membrane models for different length and time scales coarse-grained coarse-grained

3 Passive endocytosis of a spherical NP: homogeneous adhesion 2R adhesion strength membrane tension membrane bending rigidity

4 Particle-membrane interaction: phase diagram for spherical NPs binding transition bound envelopment transition SIZE unbound endocytosed adhesion strength

5 Predicting NP wrapping by deformationenergy calculations 100 nm S. Dasgupta et al., Soft Matter 9, 5473 (2013)

6 Passive endocytosis of superegg NPs SW submarine orientation rocket orientation DW n=4 n=6 Dasgupta, Auth, Gompper, Nano Letters 14, 687 (2014)

7 Passive endocytosis of cube-like NPs shallow wrapped (SW) deep wrapped (DW) two stable partially-wrapped states with shallow and deep wrapping are found for Hauser s cube Dasgupta, Auth, Gompper, Nano Letters 14, 687 (2014)

8 Dasgupta, Auth, Gompper, Nano Letters 14, 687 (2014) Passive endocytosis of cube-like NPs: phase diagram binding at vanishing adhesion strength two discontinuous transitions between shallow-wrapped, deep-wrapped, and completely-wrapped state adhesion strength

9 Systematic characterisation for interaction of NPs with homogeneous membranes spherical, ellipsoidal, cube-like, spherocylindrical, and rod-like particles membrane bending rigidity and tension continuous and discontinuous transitions rocket and submarine orientation of elongated particles Dasgupta, Auth, Gompper, Nano Letters 14, 687 (2014)

10 Biological membranes are multi-component membranes: receptor-mediated wrapping ligand receptor U binding energy per receptor ligand bond N receptors N B N A S=S A +S B sites S A S A S B 10 (figure courtesy of Karandeep Singh)

11 Receptor free energy number of sites for the receptor bound to the particle number of sites for the receptor on the free membrane binding energy per receptor number of free receptors number of bound receptors energy gain for receptor-ligand bonds and receptor entropy determine number of bound receptors 11

12 Number of bound receptors 100 nm 45 nm 27 nm smooth because of receptor entropy U = 10 kt using the same number of receptors per particle, large particles get wrapped less than small particles 12

13 Energy of receptor-ligand bonds U = 10 kt 100 nm 27 nm 45 nm receptor-ligand bond energy and membrane deformation energy lead to stable partially-wrapped states using the same number of receptors per particle, large particles get wrapped less than small particles 13

14 Receptor-limited partially-wrapped states partially-wrapped particles, lack of receptors completely-wrapped particles unbound particles receptor density partially-wrapped states occur for low receptor densities and high receptor-ligand bond energies

15 Electrostatic energy between charged NPs and charged membranes unbound particles oppositely charged NPs are attracted by charged membranes, like-charged NPs are repelled completely-wrapped particles

16 Electrostatic energy between charged NPs and charged membranes unbound particles no linear superposition for effect of positively and negatively charged lipids on NP attraction completely-wrapped particles

17 Wrapping diagram for charged NPs and membranes wrapping fraction completely-wrapped particles unbound particles charged NPs are attracted by overall neutral membranes

18 Understanding descriptors for interaction of engineered nanoparticles with membranes shape and size For homogeneous adhesion strength larger NPs are taken up easier, nonspherical NPs stick better to the membrane. softness NP softness favours membrane -bound states. surface characteristics (including a corona) Partially-wrapped membranebound states are found for lack of receptors. Systematic characterisation of NP-membrane interaction may help to understand QNAR risk assessment Dasgupta, Auth, Gompper, Nano Letters 14, 687 (2014)