Like-Charged Biomolecules Can Attract Each Other

Like-charged biomolecules can attract each other, in a biophysics phenomenon that has fascinating analogies to superconductivity. Newly obtained insights into biomolecular "like-charge attraction" may eventually help lead to improved treatments for cystic fibrosis, more efficient gene therapy and better water purification. The like-charge phenomenon occurs in "polyelectrolytes," molecules such as DNA and many proteins that possess an electric charge in a water solution. Under the right conditions, polyelectrolytes of the same type, such as groups of DNA molecules, can attract each other even though each molecule has the same sign of electric charge. Since the late 1960s, researchers have known that like-charge attraction occurs through the actions of "counterions," small ions also present in the water solution but having the opposite sign of charge as the biomolecule of interest. But they have not been able to pin down the exact details of the phenomenon. To uncover the mechanism behind like-charge attraction, a group of experimenters (led by Gerard Wong, Univ of Illinois at Urbana-Champaign, 217-265-5254) found that counterions organize themselves into columns of charge between the protein rods. Along these 'columns', the ions are not uniformly distributed, but rather are organized into frozen "charge density waves."

Remarkably, these tiny ions cause the comparatively huge actin molecule to twist, by 4 degrees for every building block (monomer) of the protein. This process has parallels to superconductivity, in which lattice distortions (phonons) mediate interactions between pairs of like-charged particles (electrons). In the case of actin, charge particles (ions) mediate attractions between like-charged distorted lattices (twisted actin helix). (Angelini et al., Proceedings of the National Academy of Sciences, July 22, 2003). In the next experiment, they investigated what kinds of counterions are needed to broker biomolecular attraction. Researchers have long known that doubly charged (divalent) ions can bring together actin proteins and viruses, and triply charged (trivalent) ions can make DNA molecules stick to one another, but monovalent ions cannot generate these effects. Studying different-sized versions of the molecule diamine (a dumbbell-shaped molecule with charged NH3 groups as the "ends" and one or more carbon atoms along the handle) to simulate the transition between divalent and monovalent ion behavior, they found that the most effective diamine counterions for causing rodlike M13 viruses to attract were the smallest ones. These small diamine molecules had a size roughly equal to the "Gouy- Chapman" length, the distance over which its electric charge exerts a significant influence. Nestled on the M13 virus surface, one end of the short diamine molecule neutralizes the virus's negative charge, while the other end supplies a positive charge that can then draw another M13 virus towards it (Butler et al., Physical Review Letters, 11 July 2003; also see Phys. Rev. Focus, 21 July 2003).

In a third experiment, researchers noticed that the like-charge attractions could cause actin molecules to organize themselves into a novel phase of liquid crystal (a structure with both liquid-like and solid-like properties). Adding small amounts of magnesium ions to a solution of actin rods caused the rods to arrange themselves into a stack of 2-dimensional rafts (see figure). This discovery may revise notions of how cells control the actin cytoskeleton.. Previously, researchers assumed that only proteins could do all the work in assembling this structure, which helps the cell to move, shape itself and divide. However, this newly discovered phase opens the possibility that physical interactions--electrostatics, electric charge, and entropy--could work synergistically with proteins to regulate the cytoskeleton in a wide range of cellular functions (Wong et al., Phys. Rev. Lett., 4 July 2003).