Novel Therapeutic Methods of Ion Transport Across Biological Membranes

Ana Moore (Inventor), Thomas Moore (Inventor)

Research output: Patent

Abstract

Transmembrane transport of protons and certain ions, such as calcium, and the control of the local concentrations of these ions in various cells are crucial to metabolic processes as in bones. Such processes play major roles in bone metabolism, muscle contraction, intercellular communication and neurotransmission, and many other biological processes. Because of the many important roles played by calcium, its metabolism is involved in a variety of diseases, including osteoarthritis, gout and related diseases, osteomalacia, and osteoporosis.For example, the transmembrane proton pumps in osteoclast cells are responsible for lowering the pH sufficiently to dissolve the bone mineral matrix which is primarily calcium carbonate and hydroxyapatite (calcium phosphate). The ruffled border region of osteoclast cells is attached to the bone providing a sealed compartment where proton pumps lower the pH to about 4, which is sufficient to solubilize hydroxyapatite resulting in osteoporosis. In another example, throughout the body Ca2+ ions act as messengers for a host of intercellular signaling events ranging from muscle contraction to vision. Calcium ions are also central players in the complex, non-linear response of cells to various stimuli and are directly involved in neurotransmission at cholinergic synapses. Because of the central role played by the equilibrium between calcium in bone structure and free in solution, its role in intercellular communication, and the current interest in assembling artificial systems that mimic non-linear behavior, it is of interest to devise ways of actively transporting Ca2+ across biological membranes. Understanding these processes and treating associated diseases would benefit greatly from the availability of a system for actively transporting calcium ions across biological membranes in a highly-controllable manner.Researchers at Arizona State University have previously succeeded in mimicking the photosynthetic proton pump in an artificial, liposome-based system. These same researchers have now devised a method to transport calcium and other ions across liposomal phospholipid membranes and build up calcium gradients across the membrane.Researchers at Arizona State University have also devised an energy-transducing artificial membrane that can be used to transport protons across a liposomal bilayer. Pumping protons across a biological membrane generates an unequal electrochemical potential of protons across the membrane. This potential, known as proton motive force (pmf), is the common denominator of essentially all bioenergetic process in living things. The generation of pmf by an artificial proton pump is significant because it provides a continuous, nearly inexhaustible, energy supply to drive biochemical processes in vitro such as synthesis, transport, molecular motors and complex, non-linear cellular signaling processes.
Original languageEnglish (US)
StatePublished - Jan 1 1900

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