Cytoskeleton and Cell Motility!
What types of cells are motile and how?
o Fibroblasts can migrate through connective tissues, helping to
rebuild damaged structures at sites of injury
o Epithelial cells lining the intestine travel up the sides of the
intestinal villi, replacing absorptive cells lost at the tip of the villus
o Cancer – cells in a primary tumour invade neighbouring tissues and
crawl into blood/ lymph vessels and then emerge at other sites in
the body to form metastases
o Neutrophils (Wiskott-Aldrich Syndrome, immunodeficiency) and
macrophages crawl to sites of infection and engulf foreign invaders
as part of the immune response
o Sperm, in different way- flagella (specialised MT-based structure –
MT, and with interspersed dyneins, moving them past each other.
Rest use actin-based cell-crawling).
o 2 ways in which neurons are migratory: early stages of nervous
system development, neurons migrate around the brain to reach
locations (e.g. neural crest cells undergo migration from their site of
origin in the neural tube to a variety of sites throughout the embryo)
OR movement of growth cone of developing axons towards their
eventual synaptic targets, to generate morphology of the neuron.
o Many cells move by crawling over surfaces rather than by using
cilia/ flagella to swim. Predatory amoebae crawl continuously in
search of food, and in animals almost all cell locomotion occurs by
crawling (with the exception of swimming sperm). During
embryogenesis, the structure of an animal is created by the
migration of individual cells to specific target locations and by the
coordinated movements of whole epithelial sheets.
How is cell crawling mediated?
In absence of cues that stabilise movement in a
particular direction, cells move randomly – projections
(filopodia and lamellipodia) extend in different
directions, and then retract. But if these extensions
sense another cell, they undergo contact inhibition –
stop upon making contact with another cell – and move
away in another direction.
Cell crawling depends on the actin-rich cortex beneath
the plasma membrane. Adhesions stabilise protrusions
– otherwise just wafted back over top of cell
, o Protrusion/extension – actin-rich plasma membrane structurs
(filopodia/ lamellipodia) are pushed out at the front of the cell
o Adhesion – actin cytoskeleton makes adhesive contact with
substrate across the plasma membrane
o Traction/ translocation – bulk of the cytoplasm/ cell body is pulled
forward following projection
o De-adhesion/ retraction of the trailing edge – trailing edge
dragged after cell in direction of movement
These stages may be distinct or may appear as a continual movement: in
some crawling cells, such as keratocytes from the fish epidermis, these
activities are closely coordinated and the cells glide forward smoothly
without changing shape, whereas in other cells such as fibroblasts, the
activities are more independent and the locomotion jerky and irregular.
Different types of cells generate different types of
protrusive structures
All are filled with a dense core of filamentous actin. The 3 structures differ
in the way in which the actin is organised and have different actin-
associated proteins.
o Filopodia (microspikes) – neuronal growth cones and some
fibroblasts. 1-dimensional, containing a long core of bundled actin
filaments
o Lamellipodia – epithelial cells, fibroblasts and some neurons. 2-
dimensional, sheet-like structures
o Invadopodia – amoeba and neutrophils. 3-dimensional structures
filled with actin filament gel
Perhaps because their 2D structure is easiest to study using a light
microscope, more information is possessed about the organisation and
mechanism of lamellipodia than the others. Invadopodia are the least
understood – thought that a ‘blob’ of the cell is projecting into a space,
followed by the remainder of the cell.
Motility is a highly co-ordinated process
Lamellipodia have been especially well studied in epithelial cells of the
epidermis of fish and frogs, which are known as keratocytes because of
their abundant keratin filaments. These cells normally form an epithelial
sheet covering the animal, and are specialised to close wounds very
rapidly. When cultured as individual cells, keratocytes assyme a
distinctive shape with a very large lamellipodium and a small, trailing cell
body (including the nucleus) that is not attached to the substrate.
Fragments of this lamellipodium can be sliced off and they continue to
crawl normally.
What types of cells are motile and how?
o Fibroblasts can migrate through connective tissues, helping to
rebuild damaged structures at sites of injury
o Epithelial cells lining the intestine travel up the sides of the
intestinal villi, replacing absorptive cells lost at the tip of the villus
o Cancer – cells in a primary tumour invade neighbouring tissues and
crawl into blood/ lymph vessels and then emerge at other sites in
the body to form metastases
o Neutrophils (Wiskott-Aldrich Syndrome, immunodeficiency) and
macrophages crawl to sites of infection and engulf foreign invaders
as part of the immune response
o Sperm, in different way- flagella (specialised MT-based structure –
MT, and with interspersed dyneins, moving them past each other.
Rest use actin-based cell-crawling).
o 2 ways in which neurons are migratory: early stages of nervous
system development, neurons migrate around the brain to reach
locations (e.g. neural crest cells undergo migration from their site of
origin in the neural tube to a variety of sites throughout the embryo)
OR movement of growth cone of developing axons towards their
eventual synaptic targets, to generate morphology of the neuron.
o Many cells move by crawling over surfaces rather than by using
cilia/ flagella to swim. Predatory amoebae crawl continuously in
search of food, and in animals almost all cell locomotion occurs by
crawling (with the exception of swimming sperm). During
embryogenesis, the structure of an animal is created by the
migration of individual cells to specific target locations and by the
coordinated movements of whole epithelial sheets.
How is cell crawling mediated?
In absence of cues that stabilise movement in a
particular direction, cells move randomly – projections
(filopodia and lamellipodia) extend in different
directions, and then retract. But if these extensions
sense another cell, they undergo contact inhibition –
stop upon making contact with another cell – and move
away in another direction.
Cell crawling depends on the actin-rich cortex beneath
the plasma membrane. Adhesions stabilise protrusions
– otherwise just wafted back over top of cell
, o Protrusion/extension – actin-rich plasma membrane structurs
(filopodia/ lamellipodia) are pushed out at the front of the cell
o Adhesion – actin cytoskeleton makes adhesive contact with
substrate across the plasma membrane
o Traction/ translocation – bulk of the cytoplasm/ cell body is pulled
forward following projection
o De-adhesion/ retraction of the trailing edge – trailing edge
dragged after cell in direction of movement
These stages may be distinct or may appear as a continual movement: in
some crawling cells, such as keratocytes from the fish epidermis, these
activities are closely coordinated and the cells glide forward smoothly
without changing shape, whereas in other cells such as fibroblasts, the
activities are more independent and the locomotion jerky and irregular.
Different types of cells generate different types of
protrusive structures
All are filled with a dense core of filamentous actin. The 3 structures differ
in the way in which the actin is organised and have different actin-
associated proteins.
o Filopodia (microspikes) – neuronal growth cones and some
fibroblasts. 1-dimensional, containing a long core of bundled actin
filaments
o Lamellipodia – epithelial cells, fibroblasts and some neurons. 2-
dimensional, sheet-like structures
o Invadopodia – amoeba and neutrophils. 3-dimensional structures
filled with actin filament gel
Perhaps because their 2D structure is easiest to study using a light
microscope, more information is possessed about the organisation and
mechanism of lamellipodia than the others. Invadopodia are the least
understood – thought that a ‘blob’ of the cell is projecting into a space,
followed by the remainder of the cell.
Motility is a highly co-ordinated process
Lamellipodia have been especially well studied in epithelial cells of the
epidermis of fish and frogs, which are known as keratocytes because of
their abundant keratin filaments. These cells normally form an epithelial
sheet covering the animal, and are specialised to close wounds very
rapidly. When cultured as individual cells, keratocytes assyme a
distinctive shape with a very large lamellipodium and a small, trailing cell
body (including the nucleus) that is not attached to the substrate.
Fragments of this lamellipodium can be sliced off and they continue to
crawl normally.
