Through the Eye of a Needle

Published in JFWTC  inhouse Journal Vol 4 Issue 3 2008 

Years ago de Gennes addressed an interesting  situation in polymer physics. Suppose a sufficiently long polymer chain in a viscous solution, has  one end anchored to the wall.   How  fast  will the free end of  chain find its way to the surface?

He  referred to this as “ Ariadne’s thread’.  The allusion was to Greek mythology, of Ariadne helping her friend Theseus to enter and escape  from the infamous maze.  The maze (Labyrinth) was  built by Daedalus the architect  to entrap the dreaded monster Minataur.  Once inside one would go endlessly along the twists and turns without ever finding the exit.  Ariadne gave a ball of thread to   Theseus  and he was to tie one end of the thread to the door post as he entered and unwind the ball as he moved straight ahead  and down (and never  be tempted to turn left  or right or up).  Theseus  thus came  to the the heart of the Labyrinth where he encounters and kills the sleeping Minotaur and  retraces his way along the threadline back to the doorpost  ( read safety and freedom) .

Well, de Gennes didn’t put any condition on where exactly the polymer terminal should appear on the surface.   What if he had?   This would have  changed a “random walk” process to a  more purposeful errand.  Any such  process then would need the machinery of “ molecualr recognition” for successful accomplishment.  This exactly is being addressed  in  the December 12^th issue of Science by  Deutman et al.    The challenge is to   coax  the   free end of a long polymer chain to thread itself through a molecular ring. 

Even in the macroscopic world it is not an easy proposition to thread a needle (especially if you wear bifocals).  You need to perfectly align the eye of the needle against the stiff tip of the thread to make the process easy and smooth.   Now you need to accomplish this at molecular level  and on top of it  the thread must find the eye of the needle  on its own ! This  has multiple biological implications  such as translocation of proteins and viruses across cell membranes.   The paper aptly titled “Mechanism of Threading a Polymer Through a Macrocyclic Ring” demonstrates this in a synthetic system.

For the eye of the needle, the team chose macrocycles  of varying ring size ( 5 to 22 atoms).   The threads were polymer chains (upto 440 atoms in length).   The threads were special in that they were knotted at one end. ( one terminal had a a bulky end group, while the other terminal was free).  Closer to the bulkier end, the chain carried a special affinity group  which could selectively recognize  and latch onto   companion group on  the outer rim of the macrocycle.   Complexation between the two groups  leads to a fluorescence signal and the team used this to monitor the kinetics of  threading.

Deutman et al have proposed possible threading mechanisms.   The  intramoleular insertion  model actually suffers a little  too much from steric  and process complexity : initial complexation of the thread and the ring and  then  looping of the chain followed by  insertion of the free end and then  the chain unlooping to stretch  and straighten out.  The thermodynamic calculations  are given,  but it isn’t very clear whether this multistep process  will pass the free energy and entropy audits.   It would be interesting to explore  the possibility of the   free terminal being  the guiding factor, rather than having the recognition site somewhere along the chain.  Another  twist to the challenge will be if  the macrocycle could sport a  molecular slit  through which the thread could  slip itself inside at  any point along the chain length.

In the same issue,  we get a peep into the  behaviour of a complex family  of  trans membrane proteins called secondary transporters,  which facilitates the passage of  small molecules and ions across the lipid bilayer.   While  substrate  molecules smoothly   roll to  the other side by  a mechanism  reminiscent of  peristaltic movement; the inhibitor moiety is stuck at the front gate itself.  Singh et al have  provided crystallographic data to support the same.

References :

1.Reptation of a polymer chain  in the Presence of Fixed Obstacles

de Gennes Journal of Chemical Physics, Vol. 55, p.572-579; 1971

2. Mechanism of Threading a Polymer Through a Macrocyclic Ring

Deutman et al Science Dec. 12, 2008   1668-1671

3. A Competitive Inhibitor Traps LeuT in an Open-to-Out Conformation.

Singh et al Science 12 December 2008: Vol. 322. no. 5908, pp. 1655 - 1661