The effect of resorcinolic lipids on biological membranes

Magdalena Siwko

Resorcinolic lipidsResorcinolic lipids

• Found in higher plants (cashew nut, Ginkgo biloba, wheat bran, rye, barley), lower plants (algae, mosses, fungi), microbial organisms (bacteria)

• Tail length (11-25) and degree of unsaturation (0-4) varies.

• Very low critical micelle concentration (CMC) 4.5-8.5M

• Potential applications: medicine, nutrition, agriculture

• Found in higher plants (cashew nut, Ginkgo biloba, wheat bran, rye, barley), lower plants (algae, mosses, fungi), microbial organisms (bacteria)

• Tail length (11-25) and degree of unsaturation (0-4) varies.

• Very low critical micelle concentration (CMC) 4.5-8.5M

• Potential applications: medicine, nutrition, agriculture

Biological activity of resorcinolsBiological activity of resorcinols

Bacteriostatic and

fungistatic activity

Non-toxic to higher

animals

Protect cellular lipids from

oxidation processes

On membranes:-pre-incorporated increase the

resistance of the liposome to

water and small solutes

-incorporated into the suspension

of liposomes increase a release

of ions, small solutes such as

glucose, change transport of

water -”surfactant-like effect”

Questions: Questions:

How resorcinolic lipids affect phospholipid bilayers? Is this dependent on the length of alkyl tail? How do resorcinols distribute within a DMPC

bilayer?

Bilayer formation in water

64 RES19

64 RES11

64 DMPC

DMPC + RES19

DMPC + RES11

DMPC +

RES25

~30-35 SPC/lipid

•Temperature: 323K

25-30mol% 28RES : 64DMPC or 112 RES : 256 DMPC

Bilayer formation RES19/DMPCBilayer formation RES19/DMPC

Mass density distributionMass density distribution

water

phosphoryl

RES

RES-OH

carbonyl

DMPC

Pure DMPC

DMPC+RES19DMPC+RES25

DMPC+RES11

Resorcinols induce packing of lipid

tails

Resorcinols induce packing of lipid

tails

SummarySummary• Bilayer formation largely unaffected by resorcinol

• Asymmetric distribution between leaflets (cluster formation) but no clear domains

• Resorcinols increase order parameters

• Interaction of RES hydroxyl groups with DMPC glycerol the ester groups

Incorporation of resorcinolic lipids in the DMPC bilayer

DMPCRES19

RES11

RES25

30mol% (21RES:64DMPC or 112RES:256DMPC)

Temperature: 323K

~35-49 SPC/lipid

Res11/DMPC bilayers (no micelle

formation)

Res11/DMPC bilayers (no micelle

formation)

Simulation time: 340 ns

0 ns 10 ns 200 ns

280 ns 300 ns

Res19/DMPC (micelle formation)

Severe membrane disruption

Res19/DMPC (micelle formation)

Severe membrane disruption

Simulation time: 175 ns

QuickTime™ and aYUV420 codec decompressor

are needed to see this picture.

Res25/DMPC (micele bilayer interaction)Formation of gel phase domain

Res25/DMPC (micele bilayer interaction)Formation of gel phase domain

Simulation time: 90 ns

QuickTime™ and aYUV420 codec decompressor

are needed to see this picture.

Steps in the pore-forming process of the incorporation

Steps in the pore-forming process of the incorporation

SummarySummary

Alternative mechanisms of incorporation lead to marked

differences in disruption.

Alternative final phases depending on chain length:

a) lamellar - RES11,

b) hexagonal - RES19,

c) lamellar with gel phase domain - RES25

Final bilayers asymmetric: much longer simulation times

required for equilibration

Alternative mechanisms of incorporation lead to marked

differences in disruption.

Alternative final phases depending on chain length:

a) lamellar - RES11,

b) hexagonal - RES19,

c) lamellar with gel phase domain - RES25

Final bilayers asymmetric: much longer simulation times

required for equilibration