Researchers at the University of Pennsylvania School of Medicine
discovered that the activity of a specific family of nanometre-sized
molecular motors called myosin-I is regulated by force. The
motor puts tension on cellular springs that allow vibrations to
be detected within the body. This finely tuned regulation has
important implications for understanding a wide variety of basic
cellular processes, including hearing and balance and glucose
uptake in response to insulin. The findings appear in the most
recent issue of Science.
'This is the first demonstration that myosin-I shows such
dramatic sensitivity to tension,' says senior author E. Michael
Ostap, Ph.D., Associate Director, Pennsylvania Muscle Institute
and Associate Professor of Physiology. 'It is surprising that a
molecular motor can sense such small changes in force.'
Myosin-I is a biological motor that uses the chemical energy
made by cells to ferry proteins within cells and to generate
force, powering the movement of molecular cargos in nearly all
In two specific cases, myosin I puts tension on the specialised
spring-like structures in human ears that enable hearing and
maintenance of balance, and also has a role in delivering the
proteins that pump glucose into cells in response to insulin.
'However, why a tension-sensing molecular motor is needed for
this function is unknown,' says Ostap.
In collaboration with Henry Shuman, PhD, Associate Professor of
Physiology, the research team used optical tweezers - a
combination focused laser beam and microscope, of sorts - to
measure incredibly small forces and movements (on the piconewton
and nanometre level) to discover that myosin I motors are
regulated by force. The motors pull on their cellular cargos
until a certain tension is attained, after which they stop
moving, but will hold the tension. If something happens in the
cell to decrease this tension, the motor will restart its
activity and will restore the lost tension.
Myosins use the energy from ATP to generate force and motion.
Humans have 40 myosin genes that sort into 12 myosin families.
Members of the myosin family have been found in every type of
cell researchers have examined. The Ostap lab is investigating
the biochemical properties of several members of the myosin
family to better understand movement in cells, which is
important in development, wound healing, the immune response,
and the spread of cancer, among other functions. These new
findings shed light on the role of myosin I in cells, supporting
the notion that this molecular motor is more important in
generating and sustaining tension rather than transporting
The research team will now apply these results to better
understand how cells use these tension sensors to carry out
their physiological functions.
from PENN Medicine