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Antibiotics & Bioelectronics poking holes in membranes

VL 11

Antibiotics (antibacterials)

• An antibacterial is a compound or substance that kills or slows down the growth of bacteria. The term is often used synonymously with the term antibiotic(s); today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic(s) has come to denote a broader range of antimicrobial compounds, including antifungal and other compounds.

• The term antibiotic was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria, but are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 2000 atomic mass units.

Poison: similar, but not selective to bacteria ….

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Bacterial cell walls are negatively charged

Lipoteichoic acids: (LTA) polysaccharides

Peptidoglycan: This is a polymer of alternating N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG)

Lipopolysaccharides(LPS)

poking holes in membranes

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Barrel stave model

Toroidal

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selection rules for antibacterial acting on cell wall

• bacterial cell walls are negative outside, while eukaryotic cells don’t have anionic lipids (PS as apoptosis marker …)

• attack bacterial membrane by cationic (+), and amphipathic peptides of proper length (cell synthesizes its own defense molecules)

• examples: ceropines, magainin, pleurocidin, …

measuring hole and pore formation: painted bilayers (or black lipid

membranes)

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bacterial resistance: many options

• reduce negative charge, e.g. by aminoarabinose

• enzymes cleave peptides (proteolytic enzymes)

• transport peptides into cell, destroy (ATP transporter)

• reduce fluidity (freeze out peptides)

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protein secondary structure may change due to interaction with membranes

some structures are pathogenic (beta-sheet), while others are not (observed for Alzheimer, Parkinson’s)

Protein-aggregates

Insoluble protein deposits in neurodegenerative disorders.

Substantia nigra of Parkinsons disease case with α-synuclein positive Lewy body (right) and Lewy neurite (left). M. Neumann, SFB 596

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a proteins with an amphipathic helix: alpha-synuclein

membrane bound form

a-S is supposed to stabilize highly curved vesicles (neurotransmitters): anti-fusiogenic function ?

a-S interaction with planar lipid membranes: x-rays

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Neutron results (Refsans at FRM-II

Molecular mechanism

Bert Nickel

a-S inserts between the negatively charged lipid headgroups this drives a phase transition to Lb phase

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membrane thinning due to helix insertion

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Electrical imaging of neuronal activity by multi-transistor-array (MTA) recording at 7.8 µm resolution

Lambacher et al.,(Fromherz group) APA 2004, 79, 1607

Bioelectronics

Organic Field Effect Transistor as readout

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The Insulated Gate Organic field effect transistor

surface charges induce band bending in the underlying semiconductor (MIS)

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Bioelectronics with supported bilayers:

Field-effect detection using phospholipid membranes

Basic idea of a dual gate OFET

change of bulk potential

change of surface potential

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AFM

Fluorescence

E. Mandaraz, BN, et al Adv. Func. Mat. 2008

Towards an electronic petri dish

Martin Göllner

Semiconductor-Electrolyte Interfaces: Materials

Pentacene (C22H14)

Tetratetracontane (TTC) (CH3(CH2)42CH3)

• good insulator:

• highly hydrophobic

• lack of π-electrons chemical inert / biocompatibile • melting point 358 - 360 K

• thermal vacuum deposition highly crystalline films

• p-type semiconductor, µ ≈ 1 cm2/Vs

• optical bandgap: 1.82 eV

• valence band edge: −5.1 eV

• instability under exposure of light, air or moisture

3

b

MV10 cm , V 20

m

M. Göllner, M. Huth, B. Nickel, Advanced Materials 22, no. 39, 4350 (2010)

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TTC: a paraffin imitate of a lipid bilayer (ion sealing)

ΔZ: 127 nm

Rq= 22.3 nm

ΔZ: 47.4 nm

Rq= 5.77 nm

7 Å/s at RT

50nm Au 50nm TTC contacts

50nm P 50nm TTC channel

θ ≈ 111°

θ ≈ 121°

M. Göllner, M. Huth, B. Nickel, Advanced Materials 22, no. 39, 4350 (2010)

a paraffin layer acts as a ca. 3.2 eV barrier for ions due to low epsilon (Born free energy)

The DGTFT-Transducer: capacitive gating via an electrolyte

M. Göllner, G. Glasbrenner, B. Nickel, Electroanalysis (2011)

dTTC = 50 nm / 250 nm

dP = 20 nm

dCOC= 8 nm

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Martin Göllner

The DGTFT-Transducer

Sensing of fatty acid molecules via bottom gate sweep

2 3

[ ], 10

[ ]apH pKR COO

R COOH H O R COO H OR COOH

M. Göllner, G. Glasbrenner, B. Nickel, Electroanalysis (2011)

bottom-gate sweep

[HA] N[cm-2]

0 0.9·1011 1.7·1011 2.6·1011

[HA] N[cm-2]

0 0.9·1011

Hexanoic acid (C6H12O2): pKa ≈ 4.8

bb P I

T b

P I

C C qNV

C C A

t

G t

I

qNV

C A

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Franz Werkmeister

flexible devices from LMU : parylene foils (3 mm) and Kapton

inspired by work of Someya and Malliaras groups

-20 -10 0 10 20

-0.30

-0.25

-0.20

-0.15

-0.10

-0.05

0.00

sweep VSD

= -5V

sweep back VSD

= -5V

sweep VSD

= -10V

sweep back VSD

= -10V

rigid

I SD [µ

A]

VG [V]

flexible transistor – parylene still on glass substrate

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-20 -10 0 10 20

-0.30

-0.25

-0.20

-0.15

-0.10

-0.05

0.00

sweep VSD

= -5V

sweep back VSD

= -5V

sweep VSD

= -10V

sweep back VSD

= -10V

flexible

I SD [µ

A]

VG [V]

pentacene transistor – removed from glass slide

J. L. Arlett, E. B. Myers, and M. L. Roukes. Comparative advantages of mechanical biosensors. Nat. Nanotechnol., 6(4):203, 2011.