Multisomes: encapsulated droplet networks
The invention provides a droplet encapsulate comprising: a drop of a hydrophobic medium; a peripheral layer of non-polymeric amphipathic molecules around the surface of the drop; and an aqueous droplet within the peripheral layer, the aqueous droplet comprising: (a) an aqueous medium and (b) an outer layer of non-polymeric amphipathic molecules around the surface of the aqueous medium. The invention also provides processes for preparing the droplet encapsulates. Various uses of the droplet encapsulates are also described, including their use as drug delivery vehicles, in synthetic biology, and in the study of membrane proteins.
1. A droplet encapsulate comprising:
a drop of a hydrophobic medium which comprises an oil;
a peripheral layer of non-polymeric amphipathic molecules around the surface of the drop; and
an aqueous droplet, or a plurality of aqueous droplets, within the peripheral layer, wherein the or each aqueous droplet comprises: (a) an aqueous medium and (b) an outer layer of non-polymeric amphipathic molecules around the surface of the aqueous medium,
wherein the droplet encapsulate comprises a bilayer of said non-polymeric amphipathic molecules, wherein said bilayer further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein, and wherein:
(i) an aqueous droplet is situated at the edge of the drop, wherein part of the outer layer of the aqueous droplet contacts said peripheral layer, thereby forming said bilayer of said non-polymeric amphipathic molecules at an interface between the aqueous droplet and the peripheral layer; or
(ii) part of the outer layer of a first of said aqueous droplets contacts part of the outer layer of a second of said aqueous droplets, thereby forming said bilayer of the non-polymeric amphipathic molecules at an interface between said first and second droplets.
2. A droplet encapsulate according to claim 1 :
(i) wherein the aqueous droplet is situated at the edge of the drop, wherein part of the outer layer of the aqueous droplet contacts said peripheral layer, thereby forming a bilayer of said non-polymeric amphipathic molecules at an interface between the aqueous droplet and the peripheral layer
(ii) wherein said bilayer further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein.
3. A droplet encapsulate according to claim 1 wherein said membrane protein is a pore protein, a channel protein or a pump protein.
4. A droplet encapsulate according to claim 1 comprising a plurality of said aqueous droplets within the peripheral layer, each aqueous droplet comprising: (a) a said aqueous medium, and (b) a said outer layer of non-polymeric amphipathic molecules around the surface of the aqueous medium.
5. A droplet encapsulate according to claim 4 , wherein part of the outer layer of a first of said aqueous droplets contacts part of the outer layer of a second of said aqueous droplets, thereby forming a bilayer of the non-polymeric amphipathic molecules at an interface between said first and second droplets, wherein said bilayer further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein.
6. A droplet encapsulate according to claim 5 wherein said membrane protein is a pore protein, a channel protein or a pump protein.
7. A droplet encapsulate according to claim 4 wherein at least one of said aqueous droplets is situated at the edge of the drop, wherein part of the outer layer of the aqueous droplet contacts the peripheral layer, thereby forming a bilayer of said non-polymeric amphipathic molecules at an interface between the aqueous droplet and the peripheral layer.
8. A droplet encapsulate according to claim 7 wherein said bilayer at the interface between said aqueous droplet and the peripheral layer further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein.
9. A droplet encapsulate according to claim 4 wherein said plurality of aqueous droplets comprises more than two aqueous droplets which are in contact with one another in a chain or network, wherein a part of the outer layer of each droplet in the chain or network contacts a part of the outer layer of another droplet in the chain or network, thereby forming bilayers of the non-polymeric amphipathic molecules at interfaces between the droplets in the chain or network.
10. A droplet encapsulate according to claim 9 wherein each of said bilayers at the interfaces between the droplets in the chain or network further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein.
11. A droplet encapsulate according to claim 9 wherein at least one of the aqueous droplets in the chain or network is situated at the edge of the drop, wherein part of the outer layer of the aqueous droplet situated at the edge of the drop contacts the peripheral layer, thereby forming a bilayer of said non-polymeric amphipathic molecules at an interface between said aqueous droplet and the peripheral layer.
12. A droplet encapsulate according to claim 11 wherein the bilayer at the interface between the aqueous droplet situated at the edge of the drop and the peripheral layer further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein.
13. A droplet encapsulate according to claim 11 wherein the bilayer at the interface between the aqueous droplet situated at the edge of the drop and the peripheral layer further comprises a membrane protein which is a pump protein, a channel protein or a pore protein.
14. A droplet encapsulate according to claim 1 wherein the oil comprises silicone oil, a hydrocarbon, or a fluorocarbon, or a mixture of two or more thereof.
15. A composition comprising: a droplet encapsulate as defined in claim 1 , or a plurality of said droplet encapsulates, and a hydrophilic carrier.
16. A protocell comprising a droplet encapsulate as defined in claim 1 , wherein said peripheral layer of non-polymeric amphipathic molecules contacts the outer layer of said aqueous droplet and thereby forms a bilayer of non-polymeric amphipathic molecules around part of the aqueous droplet.
17. A prototissue comprising a droplet encapsulate as defined in claim 4 , which droplet encapsulate comprises a plurality of said aqueous droplets, wherein the peripheral layer of non-polymeric amphipathic molecules contacts the outer layers of said aqueous droplets, thereby forming a bilayer of said non-polymeric amphipathic molecules around at least part of the surface of the plurality of aqueous droplets.
18. A sensor, battery, or electrical device comprising a droplet encapsulate as defined in claim 1 .
19. A process for producing a droplet encapsulate, which droplet encapsulate comprises:
a drop of a hydrophobic medium which comprises an oil;
a peripheral layer of non-polymeric amphipathic molecules around the surface of the drop; and
an aqueous droplet, or a plurality of aqueous droplets, within the peripheral layer, wherein the or each aqueous droplet comprises: (a) an aqueous medium and (b) an outer layer of non-polymeric amphipathic molecules around the surface of the aqueous medium,
wherein the droplet encapsulate comprises a bilayer of said non-polymeric amphipathic molecules, wherein said bilayer further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein, and wherein:
(i) an aqueous droplet is situated at the edge of the drop, wherein part of the outer layer of the aqueous droplet contacts said peripheral layer, thereby forming said bilayer of said non-polymeric amphipathic molecules at an interface between the aqueous droplet and the peripheral layer; or
(ii) part of the outer layer of a first of said aqueous droplets contacts part of the outer layer of a second of said aqueous droplets, thereby forming said bilayer of the non-polymeric amphipathic molecules at an interface between said first and second droplets;
which process comprises:
transferring an aqueous droplet, which aqueous droplet comprises (a) an aqueous medium and (b) an outer layer of non-polymeric amphipathic molecules around the surface of the aqueous medium,
into a drop of a hydrophobic medium, which drop of said hydrophobic medium has a peripheral layer of non-polymeric amphipathic molecules around its surface.
20. A process for producing a droplet encapsulate, which process comprises:
(i) introducing a droplet of aqueous medium from a first channel of a microfluidic device, which first channel contains said aqueous medium, into a second channel of the microfluidic device, which second channel contains a hydrophobic medium which comprises an oil,
wherein the aqueous medium in the first channel, or the hydrophobic medium in the second channel, or both, further comprise non-polymeric amphipathic molecules,
thereby producing in the second channel an aqueous droplet within the hydrophobic medium, said aqueous droplet comprising: (a) said aqueous medium and (b) an outer layer of said non-polymeric amphipathic molecules around the surface of the aqueous medium; and
(ii) introducing a drop of said hydrophobic medium from the second channel, which drop of hydrophobic medium comprises the aqueous droplet, or a plurality of said aqueous droplets, into a third channel of the microfluidic device, wherein the third channel contains a hydrophilic carrier,
wherein the hydrophobic medium in the second channel, or the hydrophilic carrier in the third channel or both, further comprise non-polymeric amphipathic molecules,
thereby producing in the third channel a droplet encapsulate within the hydrophilic carrier, the droplet encapsulate comprising:
the drop of said hydrophobic medium;
a peripheral layer of non-polymeric amphipathic molecules around the surface of the drop; and
said aqueous droplet, or said plurality of said aqueous droplets, within said peripheral layer,
wherein the droplet encapsulate comprises a bilayer of said non-polymeric amphipathic molecules, wherein said bilayer further comprises a membrane protein selected from a pump protein, a channel protein, a pore protein, a receptor protein, a transporter protein, a cell-recognition protein or a cell-to-cell interaction protein, and wherein:
(i) an aqueous droplet is situated at the edge of the drop, wherein part of the outer layer of the aqueous droplet contacts said peripheral layer, thereby forming said bilayer of said non-polymeric amphipathic molecules at an interface between the aqueous droplet and the peripheral layer; or
(ii) part of the outer layer of a first of said aqueous droplets contacts part of the outer layer of a second of said aqueous droplets, thereby forming said bilayer of the non-polymeric amphipathic molecules at an interface between said first and second droplets.