• UCSBgauchos twitter avatar
    Softball: Gauchos Split Final Road Games at Hawai'i https://t.co/CpEDdmmhVc
    8 hours 48 min ago
  • UCSBgauchos twitter avatar
    Gauchos are live on @ESPN3 ! WATCH >>> https://t.co/io6ZzYs9Hg https://t.co/BEO8wTxv62
    13 hours 55 min ago
  • ucsantabarbara twitter avatar
    Congrats to Leah Foltz for winning the #UCSB Grad Slam! Now she moves onto the UC-wide competition in SF on May 4th! https://t.co/kVqCtOTWb7
    20 hours 49 min ago
  • UCSBgauchos twitter avatar
    Former @UCSB_Baseball LHP Dom Mazza speaks with his hometown paper after throwing a perfecto this week! https://t.co/GPc3B3qL9g
    21 hours 8 min ago
  • ArtsandLectures twitter avatar
    Watch pianist #MurrayPerahia's breathtaking and imaginative performance, tonight at 7PM at UCSB Campbell Hall!… https://t.co/M83EeA6Y53
    23 hours 54 min ago
  • UCSBgauchos twitter avatar
    Softball: Hawai'i Tops UCSB 5-1 in Gauchos' Final Road Series Opener https://t.co/ejf0MWM1g0
    1 day 7 hours ago
  • UCSBgauchos twitter avatar
    Gauchos Sweep Past UCI 4-0 https://t.co/WFwbxDV8eA
    1 day 9 hours ago
  • ucsantabarbara twitter avatar
    We're happy to see you back, alumni! Don't miss the great events we have this weekend. #AllGauchoReunion… https://t.co/Sbz4iirr7i
    1 day 13 hours ago
  • UCSBgauchos twitter avatar
    Women's Tennis: Cal Poly 0, UC Santa Barb. 4 (Final) No.2 UCSB blanks No.7 Cal Poly in Big West Quarterfinal 4-0 https://t.co/m4kdACQFo5
    1 day 13 hours ago
  • UCSBgauchos twitter avatar
    .@UCSB_Baseball vs. UC Riverside on @ESPN3 is live now! Watch here >>> https://t.co/QJMvNLa0mQ
    1 day 13 hours ago
  • UCSBgauchos twitter avatar
    WWP: Defending Big West Champs Defeated by No. 12 LBSU in Another Overtime Match https://t.co/XIO3RJdo9p
    1 day 14 hours ago
  • UCSBgauchos twitter avatar
    Top-Seeded UCSB Set to Host Big West Golf Championship at Sandpiper GC https://t.co/SyXPKB2Ur5
    1 day 15 hours ago
  • UCSBLibrary twitter avatar
    RT @ForestSways: CEMA poster preservation for primary source research. #Chicanohertiage @Marikhasmanyan @UCSBLibrary #sca17 https://t.co/M…
    1 day 17 hours ago
  • UCSBLibrary twitter avatar
    @AmldavisAnn We're glad you're interested in using, please contact (805) 893-3062 or @library.ucsb.edu">special@library.ucsb.edu for m… https://t.co/fwAVOMoWyB
    1 day 17 hours ago
  • UCSB_GradPost twitter avatar
    CPT F-1 Visa workshop for international students on May 11 https://t.co/l6xZEndRVl #UCSB #ucsbgradpost
    1 day 18 hours ago

Which Way is Up?

UCSB study shows that key protein in epithelial cells plays important roles in how cells sense direction
Thursday, May 22, 2014 - 09:15
Santa Barbara, CA

What do sled dogs and cell clusters have in common? According to research by UC Santa Barbara’s Denise Montell, they both travel in groups and need a leader to make sure they all follow in the same direction.

Montell, Duggan Professor of Molecular Cellular and Developmental Biology, and colleagues worked on three independent projects involving E-cadherin, a protein found in epithelial cells throughout the body. The researchers used fruit-fly ovaries to uncover the role played by E-cadherin in collective cell migration. Their findings are reported today in the journal Cell.

According to traditional scientific dogma, E-cadherin acts like the mortar between bricks, holding cells together and preventing motility. Montell’s team found the opposite: Cadherin is actually promoting the ability of cells to move and migrate. “It’s doing it in three different ways in three different parts of the cell,” Montell said. “In each spot in the cell, cadherin is doing something different and all of those function together to orchestrate the movement of cells.”

Montell’s team sought to understand the E-cadherin-mediated migration of these cells with three separate approaches that converged on one idea: the guidance of cell movement. “This kind of motility is similar to what tumor cells do when they metastasize,” Montell said, “and it’s part of the normal development of different tissues.”

One researcher studied the interaction between the lead cell and the following cells; hence, the sled-dog analogy. The lead cell is tethered by E-caderin to other cells in the cluster and pulls them in the proper direction in the same way the lead sled dog guides its team.

While E-cadherin is distributed throughout the cell cluster, the lead cell — determined by the strong force of E-cadherin that causes the cell to protrude in the direction of the movement — can communicate with the side and rear cells and prohibit them from protruding. This creates a front and back to the entire cluster of cells.

Lead author Danfeng Cai, a graduate student in the Denise Montell Lab, suppressed cadherin in different cell types and analyzed the visible guidance defects by making movies of the migrating cells. When cells lacked E-cadherin, they were unable to migrate as an organized group, and the direction of their movement was random and irregular.

Another member of the research team designed an optical sensor of mechanical tension — a kind of microscopic spring — and inserted it into the cadherin protein. This enabled the measurement of force on the E-cadherin molecules. The results showed that even though the distribution of the protein was uniform, the force per molecule was stronger at the front. “It’s kind of amazing that you can make that measurement in living cells,” Montell said.

In addition to highlighting E-cadherin’s role in cell migration, the paper introduces new experimental tools the team used to probe and analyze E-cadherin in living tissue, the first being the optical sensor of mechanical tension. The researchers found that E-cadherin molecules implanted with the sensor were fully functional. This allowed them to generate transgenic flies containing only E-cadherin molecules with optical sensors.

“This in vivo tension sensor could revolutionize the area of research that strives to elucidate the interplay between biochemical signals and mechanical forces during morphogenesis,” Montell said. “In contrast to other approaches that attempt to measure forces in tissues, such as laser cutting, this one is nonperturbing.”

A second tool Montell’s team developed and reported for the first time is morphodynamic profiling. This quantitative approach allowed the researchers to compare changing cell morphologies over time between different genotypes.

Data from the cell movement imaging were mathematically translated into graphs showing cell protrusion and retraction velocities at different points in time. An analysis of 26 parameters showed that the E-cadherin and the chemoattractant receptors thought to be the guiding cell movement had statistically indistinguishable phenotypes, indicating that E-cadherin and the classic guidance receptors function in the same pathway.

“E-cadherin is serving multiple purposes,” Montell concluded, “all of which function together to coordinate the collective ability of these cells to sense direction. Our work demonstrates three completely different approaches that all show the same result.” While E-cadherin serves different functions in different subcellular locations, it appears to drive cohesive cell migration, an entirely new role for this much-studied molecule.

Contact Info: 

Julie Cohen
julie.cohen@ucsb.edu
(805) 893-7220

Topics: